Wyss is the ninja institute: it’s everywhere and anywhere, but only other ninjas can detect it. Of course it’s deeply involved with Covid and the jabs too. This piece of their work is over a decade old, but you can easily see how it plays out in the 2020’s.
Wyss Institute Develops New Nanodevice Manufacturing Strategy Using Self-Assembling DNA “Building Blocks”
May 30, 2012
Novel technology could enable new tools for delivering drugs directly to disease sites in the body
Researchers at the Wyss Institute have developed a method for building complex nanostructures out of short synthetic strands of DNA. Called single-stranded tiles (SSTs), these interlocking DNA “building blocks,” akin to Legos®, can be programmed to assemble themselves into precisely designed shapes, such as letters and emoticons. Further development of the technology could enable the creation of new nanoscale devices, such as those that deliver drugs directly to disease sites.
The technology, which is described in today’s online issue of Nature, was developed by a research team led by Wyss core faculty member Peng Yin, Ph.D., who is also an Assistant Professor of Systems Biology at Harvard Medical School. Other team members included Wyss Postdoctoral Fellow Bryan Wei, Ph.D., and graduate student Mingjie Dai.
DNA is best known as a keeper of genetic information. But in an emerging field of science known as DNA nanotechnology, it is being explored for use as a material with which to build tiny, programmable structures for diverse applications. To date, most research has focused on the use of a single long biological strand of DNA, which acts as a backbone along which smaller strands bind to its many different segments, to create shapes. This method, called DNA origami, is also being pursued at the Wyss Institute under the leadership of Core Faculty member William Shih, Ph.D. Shih is also an Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute.
Wyss researchers have built numerals, letters, and a number of other structures using short strands of DNA as building blocks.
In focusing on the use of short strands of synthetic DNA and avoiding the long scaffold strand, Yin’s team developed an alternative building method. Each SST is a single, short strand of DNA. One tile will interlock with another tile, if it has a complementary sequence of DNA. If there are no complementary matches, the blocks do not connect. In this way, a collection of tiles can assemble itself into specific, predetermined shapes through a series of interlocking local connections.
In demonstrating the method, the researchers created just over one hundred different designs, including Chinese characters, numbers, and fonts, using hundreds of tiles for a single structure of 100 nanometers (billionths of a meter) in size. The approach is simple, robust, and versatile.
As synthetically based materials, the SSTs could have some important applications in medicine. SSTs could organize themselves into drug-delivery machines that maintain their structural integrity until they reach specific cell targets, and because they are synthetic, can be made highly biocompatible.
“Use of DNA nanotechnology to create programmable nanodevices is an important focus at the Wyss Institute, because we believe so strongly in its potential to produce a paradigm-shifting approach to development of new diagnostics and therapeutics,” said Wyss Founding Director, Donald Ingber, M.D., Ph.D.
The research was supported by the Office of Naval Research, the National Science Foundation, the National Institutes of Health, and the Wyss Institute at Harvard University.
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We gave up on our profit shares from masks, if you want to help us, please use the donation button! We think frequent mask use, even short term use can be bad for you, but if you have no way around them, at least send a message of consciousness. Get it here!
I can’t find the irony because I’m distracted by the facts. The highlights in the text are mine, they are the key.
Flipping a Switch Inside the Head
With new technology, scientists are able to exert wireless control over brain cells of mice with just the push of a button. The first thing they did was make the mice hungry.
By W. Wayt Gibbs, APRIL 1, 2017
READY YOUR TINFOIL HATS—mind control is not as far-fetched an idea as it may seem. In Jeffrey M. Friedman’s laboratory, it happens all the time, though the subjects are mice, not people.
Friedman and his colleagues have demonstrated a radio-operated remote control for the appetite and glucose metabolism of mice—a sophisticated technique to wirelessly alter neurons in the animals’ brains. At the flick of a switch, they are able to make mice hungry—or suppress their appetite—while the mice go about their lives normally. It’s a tool they are using to unravel the neurological basis of eating, and it is likely to have applications for studies of other hard-wired behaviors.
Friedman, Marilyn M. Simpson Professor, has been working on the technique for several years with Sarah Stanley, a former postdoc in his lab who now is assistant professor at the Icahn School of Medicine at Mount Sinai, and collaborators at Rensselaer Polytechnic Institute. Aware of the limitations of existing methods for triggering brain cells in living animals, the group set out to invent a new way. An ideal approach, they reasoned, would be as noninvasive and non-damaging as possible. And it should work quickly and repeatedly.
Although there are other ways to deliver signals to neurons, each has its limitations. In deep-brain stimulation, for example, scientists thread a wire through the brain to place an electrode next to the target cells. But the implant can damage nearby cells and tissues in ways that interfere with normal behavior. Optogenetics, which works similarly but uses fiber optics and a pulse of light rather than electricity, has the same issue. A third strategy—using drugs to activate genetically modified cells bred into mice—is less invasive, but drugs are slow to take effect and wear off.
The solution that Friedman’s group hit upon, referred to as radiogenetics or magnetogenetics, avoids these problems. With their method, published last year in Nature, biologists can turn neurons on or off in a live animal at will—quickly, repeatedly, and without implants—by engineering the cells to make them receptive to radio waves or a magnetic field.
“In effect, we created a perceptual illusion that the animal had a drop in blood sugar.”
“We’ve combined molecules already used in cells for other purposes in a manner that allows an invisible force to take control of an instinct as primal as hunger,” Friedman says.
The method links five very different biological tools, which can look whimsically convoluted, like a Rube Goldberg contraption on a molecular scale. It relies on a green fluorescent protein borrowed from jellyfish, a peculiar antibody derived from camels, squishy bags of iron particles, and the cellular equivalent of a door made from a membrane-piercing protein—all delivered and installed by a genetically engineered virus. The remote control for this contraption is a modified welding tool (though a store-bought magnet also works).
The researchers’ first challenge was to find something in a neuron that could serve as an antenna to detect the incoming radio signal or magnetic field. The logical choice was ferritin, a protein that stores iron in cells in balloon-like particles just a dozen nanometers wide. Iron is essential to cells but can also be toxic, so it is sequestered in ferritin particles until it is needed. Each ferritin particle carries within it thousands of grains of iron that wiggle around in response to a radio signal, and shift and align when immersed in a magnetic field. We all have these particles shimmying around inside our brain cells, but the motions normally have no effect on neurons.
Friedman and Stanley, with equipment they use to send radio waves. Photo by Zachary Veilleux
Friedman’s team realized that they could use a genetically engineered virus to create doorways into a neuron’s outer membrane. If they could then somehow attach each door to a ferritin particle, they reasoned, they might be able to wiggle the ferritin enough to jostle the door open. “The ‘door’ we chose is called TRPV1,” says Stanley. “Once TRPV1 is activated, calcium and sodium ions would next flow into the cell and trigger the neuron to fire.” The bits borrowed from camels and jellyfish provided what the scientists needed to connect the door to the ferritin (see How to outfit a brain sidebar, right).
Once the team had the new control mechanism working, they put it to the test. For Friedman and Stanley, whose goal is to unravel the biological causes of overeating and obesity, the first application was obvious: Try to identify specific neurons involved in appetite. The group modified glucose-sensing neurons—cells that are believed to monitor blood sugar levels in the brain and keep them within normal range—to put them under wireless control. To accomplish this, they inserted the TRPV1 and ferritin genes into a virus and—using yet another genetic trick—injected them into the glucose-sensing neurons. They could then fiddle with the cells to see whether they are involved, as suspected, in coordinating feeding and the release of hormones, such as insulin and glucagon, that keep blood glucose levels in check.
HOW TO OUTFIT A BRAIN FOR RADIO CONTROL Scientists have come up with a clever way to control neurons via radio by cobbling together genes from humans, camels, and jellyfish. They use an engineered virus to install a door into each target neuron’s outer membrane, then jostle the door open using ferritin particles that respond to strong radio signals. Once the door opens, calcium ions pour into the cell and trigger the neuron to fire. 1. To install the radiogenetics system into neurons, the scientists equipped an adenovirus with the various genes needed to make the system work. Then they squirted the modified virus onto the brain cells they wanted to alter. 2. One of the added genes produces TRPV1, a protein that normally helps cells detect heat and motion. Within each neuron, the TRPV1 protein (pink) embeds itself into the cell’s outer membrane. Like a door, it can change shape to open or shut an ion channel. To add a knob to the door, the researchers stitched TRPV1 to a “nanobody” (violet)—an unusually simple variety of antibody found in camels. 3. Iron-filled ferritin particles (green) serve as the system’s sensor. To allow them to grab onto the nanobody doorknob, the researchers tacked on a gene for GFP—a jellyfish protein that glows green under ultraviolet light. By design, the nanobody and GFP stick together tightly. The system is now connected. When exposed to strong radio waves or magnetic fields, the ferritin particles wiggle, the ion channel opens, and calcium ions (red) flow in to activate the cell.
Once the virus had enough time to infect and transform the target neurons, the researchers switched on a radio transmitter tuned to 465 kHz, a little below the band used for AM radio.
The neurons responded. They began to fire, signaling a shortage of glucose even though the animal’s blood sugar levels were normal. And other parts of the body responded just as they would to a real drop in blood sugar: insulin levels fell, the liver started pumping out more glucose, and the animals started eating more. “In effect,” Friedman says, “we created a perceptual illusion that the animal had low blood glucose even though the levels were normal.”
Inspired by these results, the researchers wondered if magnetism, like radio waves, might trigger ferritin to open the cellular doors. It did: When the team put the mice cages close to an MRI machine, or waved a rare-earth magnet over the animals, their glucose-sensing neurons were triggered.
Stimulating appetite is one thing. Could they also suppress it? The group tweaked the TRPV1 gene so it would pass chloride, which acts to inhibit neurons. Now when they inserted the modified TRPV1 into the neurons, the rush of chloride made the neurons behave as if the blood was overloaded with glucose. Insulin production surged in the animals, and they ate less. “This seems to indicate clearly that the brain as well as the pancreas is involved in glucose regulation,” Friedman says.
Friedman and Stanley hope that biologists will be able to use the remote-control system to tackle a range of neural processes other than appetite. And beyond being a basic research tool, the method could potentially lead to novel therapies for brain disorders.
For example, one could imagine using it to treat Parkinson’s disease or essential tremor—conditions that are sometimes treated by deep brain stimulation, via wires implanted into patients’ brains and connected to a battery pack tucked into the chest. Potentially, it would be less invasive to inject the crippled virus into the same spot of the brain and let it permanently modify the cells there, making them responsive to wireless control.
In theory, it might also be possible to make a patient’s own cells receptive to electromagnetic waves by removing them from the body, delivering TRPV1 and ferritin, and then putting the cells back, Friedman says. This would be a protocol not unlike those currently used in stem cell treatments and some cancer immunotherapies, in which patients’ own cells are engineered and reimplanted back into their bodies.
At this point, however, the system’s clinical usefulness is a question of speculation. “We are a long way from using it in humans for medical treatments,” Friedman says. “Much would need to be done before it could even be tested.”
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! Articles can always be subject of later editing as a way of perfecting them
The latest piece of evidence to confirm many of the revelations we’ve published for the past year or so. You have to read back to get more of the picture we’re about to sketch here.
We can’t offer informed consent for these experiments conducted on us because we are not offered much information. Only rich people can access some of it at prices most of us can’t dream. Maybe you can, or maybe people start donating enough so we can afford surviving another month and buying this info for the purpose of making it freely available to everyone, as it should be.
What am I talking about is the book pictured in our cover illustration and detailed below, which costs well over 1000$!
More precisely $1185 just for a single license PDF, the hardcover print would cost you about 100 more.
Why is this thing so expensive, you may ask?
THESE INFORMATIONS ARE SO EXPENSIVE EXACTLY TO BE PROHIBITIVE TO THE PLEBS AND OFFER A LEVERAGE OVER THOSE WHO ARE KEPT OUT OF THE LOOP, IN THE DARK
Predictably so, but:
These informations also must to have the highest degree of accuracy in order to sell as expensively!
Superb quality book delivered in a timely fashion with full financial documentation received via email.
Testimonial by Dr Tom Kidd, Associate Professor, University of Nevada
Bonus for us, this book is from May 2020, so it must have been elaborated prior to April 2020. This means it might be outdated by now for investors, but witty investigators like us find an advantage in this:
THE BOOK HAS BEEN ELABORATED WITH BEHIND THE SCENES SCIENCE ON THE INDUSTRIES WHICH, IN TURN MUST HAVE HAD PRE-SCIENCE ON THE PLANDEMIC! There was no publicly available information in March to build such a book, and the industries they talk about must have been prescient, way ahead of the writers. Only the fact that this book existed in May 2020 is single-handedly proving there was a whole lot of awareness in some industries about the pandemic. Corroborated with all other evidence we’ve provided on this website, pandemic pre-planning, ergo pre-science, becomes a certitude.
Until plebs learn the GameStop lesson properly and start associating their financial power to break this classism and this information gatekeeping, we have to be happy with whatever meat we can chew from the bones they throw out. Luckily for you, I can show you how to suck a bone dry and use it to find more. It’s not going to be a full course, but it might become more than most people can load up.
Let’s start with the description (highlights are mine):
“Nanotechnology and nanomaterials can significantly address the many clinical and public healthcare challenges that have arisen from the coronavirus pandemic. This analysis examines in detail how nanotechnology and nanomaterials can help in the fight against this pandemic disease, and ongoing mitigation strategies. Nano-based products are currently being developed and deployed for the containment, diagnosis, and treatment of Covid-19.
Nanotechnology and nanomaterials promise:
Improved and virus disabling air filtration.
Low-cost, scalable detection methods for the detection of viral particles
Enhanced personal protection equipment (PPE) including facemasks.
New antiviral vaccine and drug delivery platforms.
New therapeutic solutions.
Report contents include:
Market analysis of nano-based diagnostic tests for COVID-19 including nanosensors incorporating gold nanoparticles, iron oxide nanoparticles, graphene, quantum dots, carbon quantum dots and carbon nanotubes. Market revenues adjusted to pandemic outcomes. In-depth company profiles. Companies profiled include Abbott Laboratories, Cardea, Ferrotec (USA) Corporation, E25Bio, Grolltex, Inc., Luminex Corporation etc.
Market analysis of antiviral and antimicrobial nanocoatings for surfaces including fabric (mask, gloves, doctor coats, curtains, bed sheet), metal (lifts, doors handle, nobs, railings, public transport), wood (furniture, floors and partition panels), concrete (hospitals, clinics and isolation wards) and plastics (switches, kitchen and home appliances).
Market revenues adjusted to pandemic outcomes. In-depth company profiles. Companies profiled include Advanced Materials-JTJ s.r.o., Bio-Fence, Bio-Gate AG, Covalon Technologies Ltd., EnvisionSQ, GrapheneCA, Integricote, Nano Came Co. Ltd., NanoTouch Materials, LLC, NitroPep and many more.
Market analysis of air-borne virus filtration including photocatalytic Nano-TiO2 filters, nanofiber filers, nanosilver, nanocellulose, graphene and carbon nanotube filtration. Market revenues adjusted to pandemic outcomes. In-depth company profiles. Companies profiled include G6 Materials, Daicel FineChem Ltd., NANOVIA s.r.o., Toray Industries, Inc., Tortech Nano Fibers etc.
Market analysis of nano-based facemask and other PPE products. Market revenues adjusted to pandemic outcomes. In-depth company profiles. Companies profiled include planarTECH LLC, RESPILON Group s. r. o., SITA, Sonovia Ltd. etc.
Nanotherapies and drug delivery vehicles currently being produced and clinical trials of vaccines for COVID-19. Market revenues adjusted to pandemic outcomes. In-depth company profiles. In-depth company profiles. Companies profiled include Arcturus Therapeutics, Inc., Arbutus Biopharma, BlueWillow Biologics, Elastrin Therapeutics Inc., EnGeneIC Ltd. etc.
Key scientific breakthroughs and developments that are underway right now.”
As you can see, the description alone offers enough evidence that embedding a whole range of nanotech in facemasks, tests, drugs and many other product.
You can bet your ass your new fridge connect to the internet and has some antimicrobial nanocoating that later will prove to be worse than DDT or asbestos, but at least it’s not gonna be Covid, right?
“You could put the computational power of the spaceship Voyager onto an object the size of a cell”. And that was back in 2018
Can we dig more clues though?
Sir, yes, sir!
I’m going to do something unusual and seemingly unpractical copying here the whole table of contents, just in case, because almost every chapter and figure title deserves to be a separate post on this website as well, besides the multitude of leads as to what to research.
1 RESEARCH SCOPE AND METHODOLOGY 1.1 Report scope 1.2 Research methodology
2 INTRODUCTION
3 DIAGNOSTIC TESTING 3.1 Nanotechnology and nanomaterials solutions 3.1.1 Current Diagnostic Tests for COVID-19 3.1.2 Emerging Diagnostic Tests for COVID-19 3.1.3 Nanosensors/nanoparticles (silver nanoclusters, Gold nanoparticles, Iron oxide nanoparticles, Quantum dot barcoding, nanowires, silica nanoparticles) 3.1.4 Carbon nanomaterials for diagnostic testing 3.2 Market revenues 3.2.1 Market estimates adjusted to pandemic demand, forecast to 2025. 3.3 Companies 3.4 Academic research
4 ANTIVIRAL AND ANTIMICROBIAL COATINGS AND SURFACES 4.1 Nanotechnology and nanomaterials solutions 4.1.1 Nanocoatings. 4.1.2 Applications 4.1.3 Anti-viral nanoparticles and nanocoatings 4.1.3.1 Reusable Personal Protective Equipment (PPE) 4.1.3.2 Wipe on coatings 4.1.4 Graphene-based coatings 4.1.4.1 Properties 4.1.4.2 Graphene oxide. 4.1.4.3 Reduced graphene oxide (rGO) 4.1.4.4 Markets and applications 4.1.5 Silicon dioxide/silica nanoparticles (Nano-SiO2) -based coatings 4.1.5.1 Properties. 4.1.5.2 Antimicrobial and antiviral activity 4.1.5.3 Easy-clean and dirt repellent 4.1.6 Nanosilver-based coatings. 4.1.6.1 Properties 4.1.6.2 Antimicrobial and antiviral activity 4.1.6.3 Markets and applications. 4.1.6.4 Commercial activity 4.1.7 Titanium dioxide nanoparticle-based coatings 4.1.7.1 Properties 4.1.7.2 Exterior and construction glass coatings 4.1.7.3 Outdoor air pollution 4.1.7.4 Interior coatings 4.1.7.5 Medical facilities 4.1.7.6 Wastewater Treatment 4.1.7.7 Antimicrobial coating indoor light activation 4.1.8 Zinc oxide nanoparticle-based coatings 4.1.8.1 Properties. 4.1.8.2 Antimicrobial activity 4.1.9 Nanocellullose (cellulose nanofibers and cellulose nanocrystals)-based coatings. 4.1.9.1 Properties 4.1.9.2 Antimicrobial activity 4.1.10 Carbon nanotube-based coatings 4.1.10.1 Properties 4.1.10.2 Antimicrobial activity 4.1.11 Fullerene-based coatings 4.1.11.1 Properties 4.1.11.2 Antimicrobial activity 4.1.12 Chitosan nanoparticle-based coatings 4.1.12.1 Properties 4.1.12.2 Wound dressings 4.1.12.3 Packaging coatings and films 4.1.12.4 Food storage 4.1.13 Copper nanoparticle-based coatings 4.1.13.1 Properties 4.1.13.2 Application in antimicrobial nanocoatings 4.2 Market revenues 4.2.1 Market revenues adjusted to pandemic demand, forecast to 2030. 4.3 Companies 4.4 Academic research
5 AIR-BORNE VIRUS FILTRATION 5.1 Nanotechnology and nanomaterials solutions (nanoparticles titanium dioxide, Polymeric nanofibers, Nanosilver, Nanocellulose, Graphene, Carbon nanotubes) 5.2 Market revenues 5.2.1 Market estimates adjusted to pandemic demand, forecast to 2025 5.3 Companies 5.4 Academic research
6 FACEMASKS AND OTHER PPE 6.1 Nanotechnology and nanomaterials solutions (Polymer nanofibers, Nanocellulose, Nanosilver, Graphene) 6.2 Market revenues 6.2.1 Market estimates adjusted to pandemic demand, forecast to 2025 6.3 Companies 6.4 Academic research
7 DRUG DELIVERY AND THERAPEUTICS 7.1 Nanotechnology and nanomaterials solutions 7.1.1 Products 7.1.2 Nanocarriers 7.1.3 Nanovaccines 7.2 Market revenues 7.2.1 Market estimates adjusted to pandemic demand, forecast to 2025 7.3 Companies 7.4 Academic research
8 REFERENCES
List of Tables Table 1. Current Diagnostic Tests for COVID-19 Table 2. Development phases of diagnostic tests Table 3. Emerging Diagnostic Tests for COVID-19 Table 4. Nanoparticles for diagnostic testing-Types of nanoparticles, properties and application Table 5. Gold nanoparticle reagent suppliers list Table 6. Carbon nanomaterials for diagnostic testing-types, properties and applications Table 7. Global revenues for nanotech-based diagnostics and testing, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates Table 8. Academic research in nano-based COVID-19 diagnostics and testing. Table 9: Anti-microbial and antiviral nanocoatings-Nanomaterials used, principles, properties and applications. Table 10. Nanomaterials utilized in antimicrobial and antiviral nanocoatings coatings-benefits and applications. Table 11: Properties of nanocoatings. Table 12: Antimicrobial and antiviral nanocoatings markets and applications Table 13: Nanomaterials used in nanocoatings and applications. Table 14: Graphene properties relevant to application in coatings Table 15. Bactericidal characters of graphene-based materials Table 16. Markets and applications for antimicrobial and antiviral nanocoatings graphene nanocoatings Table 17. Markets and applications for antimicrobial and antiviral nanosilver coatings. Table 18. Commercial activity in antimicrobial nanosilver nanocoatings Table 19. Antibacterial effects of ZnO NPs in different bacterial species. Table 20. Types of carbon-based nanoparticles as antimicrobial agent, their mechanisms of action and characteristics Table 21. Mechanism of chitosan antimicrobial action Table 22. Global revenues for antimicrobial and antiviral nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates. Table 23. Global revenues for Anti-fouling & easy clean nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates. Table 24. Global revenues for self-cleaning (bionic) nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Table 25. Global revenues for self-cleaning (photocatalytic) nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Table 26. Antimicrobial, antiviral and antifungal nanocoatings research in academia Table 27. Cellulose nanofibers (CNF) membranes Table 28: Comparison of CNT membranes with other membrane technologies Table 29. Nanomaterials in air-borne virus filtration-properties and applications Table 30. Global revenues for nanotech-based air-borne virus filtration, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates Table 31: Oji Holdings CNF products Table 32. Academic research in nano-based air-borne virus filtration Table 33. Nanomaterials in facemasks and other PPE-properties and applications Table 34. Global revenues for nanotech-based facemasks and PPE, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates Table 35. Academic research in nano-based facemasks and other PPE Table 36. Applications in drug delivery and therapeutics, by nanomaterials type-properties and applications Table 37. Nanotechnology drug products Table 38. List of antigens delivered by using different nanocarriers Table 39. Nanoparticle-based vaccines Table 40. Global revenues for nano-based drug delivery and therapeutics, 2019-2030, billion US$, adjusted for COVID-19 related demand, conservative and high estimates Table 41. Academic research in nano-based drug delivery and therapeutics to address COVD-19
List of Figures Figure 1. Anatomy of COVID-19 Virus Figure 2. Graphene-based sensors for health monitoring Figure 3. Schematic of COVID-19 FET sensor incorporating graphene Figure 4. Global revenues for nanotech-based diagnostics and testing, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 5. Printed graphene biosensors Figure 6. AGILE R100 system Figure 7. nano-screenMAG particles Figure 8. GFET sensors. Figure 9. DNA endonuclease-targeted CRISPR trans reporter (DETECTR) system Figure 10. SGTi-flex COVID-19 IgM/IgG Figure 11. Schematic of anti-viral coating using nano-actives for inactivation of any adhered virus on the surfaces Figure 12: Graphair membrane coating Figure 13: Antimicrobial activity of Graphene oxide (GO) Figure 14. Nano-coated self-cleaning touchscreen Figure 15: Hydrophobic easy-to-clean coating Figure 16 Anti-bacterial mechanism of silver nanoparticle coating. Figure 17: Mechanism of photocatalysis on a surface treated with TiO2 nanoparticles Figure 18: Schematic showing the self-cleaning phenomena on superhydrophilic surface. Figure 19: Titanium dioxide-coated glass (left) and ordinary glass (right). Figure 20: Self-Cleaning mechanism utilizing photooxidation. Figure 21: Schematic of photocatalytic air purifying pavement. Figure 22: Schematic of photocatalytic water purification Figure 23. Schematic of antibacterial activity of ZnO NPs Figure 24: Types of nanocellulose Figure 25. Mechanism of antimicrobial activity of carbon nanotubes Figure 26: Fullerene schematic Figure 27. TEM images of Burkholderia seminalis treated with (a, c) buffer (control) and (b, d) 2.0 mg/mL chitosan; (A: additional layer; B: membrane damage) Figure 28. Global revenues for antimicrobial and antiviral nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 29. Global revenues for anti-fouling and easy-to-clean nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 30. Global revenues for self-cleaning (bionic) nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 31. Global revenues for self-cleaning (photocatalytic) nanocoatings, 2019-2030, US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 32. Lab tests on DSP coatings Figure 33. GrapheneCA anti-bacterial and anti-viral coating Figure 34. Microlyte® Matrix bandage for surgical wounds Figure 35. Self-cleaning nanocoating applied to face masks. Figure 36. NanoSeptic surfaces. Figure 37. NascNanoTechnology personnel shown applying MEDICOAT to airport luggage carts Figure 38. Basic principle of photocatalyst TiO2 Figure 39. Schematic of photocatalytic indoor air purification filter. Figure 40. Global revenues for nanotech-based air-borne virus filtration, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates. Figure 41. Multi-layered cross section of CNF-nw Figure 42: Properties of Asahi Kasei cellulose nanofiber nonwoven fabric Figure 43: CNF nonwoven fabric Figure 44: CNF gel.. Figure 45. CNF clear sheets Figure 46. Graphene anti-smog mask Figure 47. Global revenues for nanotech-based facemasks and PPE, 2019-2030, millions US$, adjusted for COVID-19 related demand, conservative and high estimates Figure 48. FNM’s nanofiber-based respiratory face mask.. Figure 49. ReSpimask® mask Figure 50. Schematic of different nanoparticles used for intranasal vaccination Figure 51. Global revenues for nano-based drug delivery and therapeutics, 2019-2030, billion US$, adjusted for COVID-19 related demand, conservative and high estimates.
So are you ready for your first “printed graphene bio-sensors”? Just picked a random item from the list above.
So what I’m going to do in the upcoming updates to this article is to follow every lead I got above, and I’m going to investigate every company they report on, as per their list below. You should do it too, independently, and compare your results with mine. It’s both science and investigative journalism, the juiciest combo.
Abbott Laboratories
Advanced Materials-JTJ s.r.o.
Arbutus Biopharma
Arcturus Therapeutics
Bio-Fence
Bio-Gate AG
BlueWillow Biologics
Cardea
Covalon Technologies Ltd.
Daicel FineChem Ltd.
E25Bio
Elastrin Therapeutics Inc.
EnGeneIC Ltd.
EnvisionSQ
Ferrotec (USA) Corporation
G6 Materials
GrapheneCA
Grolltex, Inc.
Integricote
Luminex Corporation
Nano Came Co. Ltd.
NanoTouch Materials, LLC
NANOVIA s.r.o.
NitroPep
RESPILON Group s. r. o.
SITA
Sonovia Ltd.
TECH LLC
Toray Industries
Tortech Nano Fibers
A taste of the future: Luminex, on of the companies listed above, makes PCR tests and stuff like magnetic micro-beads. They’ve just been bought for almost $2B by some Italians who can afford $1000+ books.
BESIDES THE DANGERS OF NANOBOTS, THIS INDUSTRY IS AN ENVIRONMENTAL CANCER AND A TOP CO2 PRODUCER
Ian Illuminato of Friends of the Earth says consumers deserve a say in nanotech regulation. JIM THOMAS/ETC GROUP
Nanotechnology was supposed to revolutionize the world, making us healthier and producing cleaner energy. But it’s starting to look more like a nightmare.
Nanomaterials—tiny particles as little as 1/100,000 the width of a human hair—have quietly been used since the 1990s in hundreds of everyday products, everything from food to baby bottles, pills, beer cans, computer keyboards, skin creams, shampoo, and clothes.
But after years of virtually unregulated use, scientists are now starting to say the most commonly used nanoproducts could be harming our health and the environment.
One of the most widespread nanoproducts is titanium dioxide. More than 5,000 tonnes of it are produced worldwide each year for use in food, toothpaste, cosmetics, paint, and paper (as a colouring agent), in medication and vitamin capsules (as a nonmedicinal filler), and in most sunscreens (for its anti-UV properties).
In food, titanium-dioxide nanoparticles are used as a whitener and brightener in confectionary products, cheeses, and sauces. Other nanoparticles are employed in flavourings and “nutritional” additives, and to reduce fat content in “health” foods.
In the journal Cancer Research in 2009, environmental-health professor Robert Schiestl coauthored the first comprehensive study of how titanium-dioxide nanoparticles affect the genes of live animals. Mice in his study suffered DNA and chromosomal damage after drinking water with the nanoparticles for five days.
“It should be removed from food and drugs, and there’s definitely no reason for it in cosmetic products,” said cancer specialist Schiestl, who is also a professor of pathology and radiation oncology at UCLA’s school of medicine.
“The study shows effects [from the nanoparticles] on all kinds of genetic endpoints,” Schiestl told the Georgia Straight in a phone interview from his office. “All those are precursor effects of cancer. It’s a wake-up call to do something.”
After Schiestl’s study came out, he said, he started getting calls from nervous people saying they had discovered titanium dioxide was listed as a nonmedicinal ingredient in their prescription medication. “They wanted to know how to get it out,” he said. “I said, ”˜I don’t know how to get it out.’ ”
Schiestl’s study is cited by groups like Greenpeace and Friends of the Earth in their calls for a moratorium on nanomaterials in food and consumer products.
“They were thought to be safe. Our study shows a lot of harm,” Schiestl said.
Nanoparticles can be harmful because they are so tiny they can pass deep into the skin, lungs, and blood. They are made by burning or crushing regular substances like titanium, silver, or iron until they turn into an ultrafine dust, which is used as a coating on, or ingredient in, various products.
Schiestl is now studying two other common nanoparticles, zinc oxide and cadmium oxide, and he has found they also cause DNA and chromosomal damage in mice.
Yet two years after Schiestl’s first study, titanium dioxide and other nanoparticles remain virtually unregulated in Canada and the U.S. Products containing nanoparticles still don’t have to be labelled, and manufacturers don’t have to prove they are safe for health or the environment.
In fact, only a small fraction of the hundreds of nanomaterials on the market have been studied to see if they are safe.
“The public has had little or no say on this. It’s mostly industry guiding government to make sure this material isn’t regulated,” said Ian Illuminato, a nanotech expert with Friends of the Earth, speaking from his home office in Victoria.
“Consumers aren’t given the right to avoid this. We think it’s dangerous and shouldn’t be in contact with the public and the environment,” he said.
Meanwhile, the number of products using nanomaterials worldwide has shot up sixfold in just a couple of years, from 212 in 2006 to more than 1,300 in 2011, according to a report in March by the Washington, D.C.–based Project on Emerging Nanotechnologies.
Those numbers are based on self-reporting by industry, and the real numbers are thought to be much higher. A Canadian government survey in 2009 found 1,600 nanoproducts available here, according to a report in December from the ETC Group, an Ottawa-based nonprofit that studies technology.
Nanotech is worth big money. More than $250 billion of nano-enabled products were produced globally in 2009, according to Lux Research, a Boston-based technology consultancy. That figure is expected to rise 10-fold, to $2.5 trillion, by 2015.
Lux Research estimated in 2006 that one-sixth of manufactured output would be based on nanotechnology by 2014.
Nanotech already appears to be affecting people’s health. In 2009, two Chinese factory workers died and another five were seriously injured in a plant that made paint containing nanoparticles.
The seven young female workers developed lung disease and rashes on their face and arms. Nanoparticles were found deep in the workers’ lungs.
“These cases arouse concern that long-term exposure to some nanoparticles without protective measures may be related to serious damage to human lungs,” wrote Chinese medical researchers in a 2009 study on the incident in the European Respiratory Journal.
When inhaled, some types of nanoparticles have been shown to act like asbestos, inflaming lung tissue and leading to cancer. In 2009, the World Health Organization’s International Agency for Cancer Research declared titanium dioxide to be “possibly carcinogenic to humans” after studies found that inhaling it in nanoparticle form caused rats to develop lung cancer and mice to suffer organ damage.
Nanoparticles can also hurt the skin. All those nanoparticles in skin creams and sunscreens may be behind a rise in eczema rates in the developed world, according to a 2009 study in the journal Experimental Biology and Medicine. The study found that titanium-dioxide nanoparticles caused mice to develop eczema. The nanoparticles “can play a significant role in the initiation and/or progression of skin diseases”, the study said.
Schiestl said nanoparticles could also be helping to fuel a rise in the rates of some cancers. He wouldn’t make a link with any specific kind of cancer, but data from the U.S. National Cancer Institute show that kidney and renal-pelvis cancer rates rose 24 percent between 2000 and 2007 in the U.S., while the rates for melanoma of the skin went up 29 percent and thyroid cancer rose 54 percent.
Schiestl said workers who deal with nanoparticles could be the most affected. That concern prompted the International Union of Food, Farm, and Hotel Workers to call in 2007 for a moratorium on commercial uses of nanotechnology in food and agriculture.
But despite all the health risks, we may already have run out of time to determine many of nanotech’s health impacts, Schiestl said.
“Nanomaterial is so ubiquitous that it would be very difficult to do an epidemiological study because there would be no control group of people who don’t use it.”
What happens when nanoparticles get out into the environment in wastewater or when products are thrown out?
Nanosilver is the most common nanomaterial on the market. Its extraordinary antimicrobial properties have earned it a place in a huge variety of products, including baby pacifiers, toothpaste, condoms, clothes, and cutting boards.
Virginia Walker, a biology professor at Queen’s University in Kingston, Ontario, decided to study nanosilver one day after a grad student said her mother had bought a new washing machine that doused clothes with silver nanoparticles to clean them better.
It sounded intriguing, Walker recalled thinking, but what would happen if nanosilver in the laundry water wound up in the environment? “What would it do to the bacterial communities out there?” she wondered.
On a whim, Walker decided to study the question. She figured the nanosilver would probably have no impact on beneficial microbes in the environment because any toxicity would be diluted.
“I did the experiment almost as a lark, not expecting to find anything,” she said by phone. “I hoped I would not find anything.”
In fact, Walker found that nanosilver was “highly toxic” to soil bacteria. It was especially toxic to one kind of nitrogen-fixing bacterium that is important to plant growth.
“If you had anything that was sensitive to nanoparticles, the last thing you would want is to have this microbe affected,” Walker said in a phone interview from her office.
The study prompted Walker to do more studies on nanoparticles. In one study now being reviewed for publication, one of her students found that mice exposed to nanoparticles developed skeletal abnormalities.
“People should have their eyes open. There are so many different nanoparticles, and the consequences of their use could be grave. We know almost nothing about these things,” Walker said.
Other scientists have raised concerns about nanosilver too. Some clothes makers now put it in socks and shirts, promising it will help control body odour. In a 2008 study in the Washington, D.C.–based journal Environmental Science and Technology, researchers took nanosilver-laced socks and washed them in water. They found the socks released up to half of their nanosilver into the water.
“If you start releasing ionic silver, it is detrimental to all aquatic biota. Once the silver ions get into the gills of fish, it’s a pretty efficient killer,” said study coauthor Troy Benn, a graduate student at Arizona State University, in a ScienceDaily.com story in 2008.
“I’ve spoken with a lot of people who don’t necessarily know what nanotechnology is, but they are out there buying products with nanoparticles in them.”
And what about the promise that nanotech could produce cleaner energy? The idea was that nanoparticles could make solar panels more efficient, be used as fuel additives to improve gas mileage, and make lighter cars and planes.
Most of the promised efficiency gains haven’t materialized, according to a 2010 report from Friends of the Earth. And it turns out that making nanomaterial is itself a huge energy guzzler.
A kilogram of carbon nanotubes—a nanoparticle used in cancer treatment and to strengthen sports equipment—requires an estimated 167 barrels of oil to produce, the Friends of the Earth report said.
Carbon nanotubes are “one of the most energy intensive materials known to humankind”, said a 2010 report to a symposium of the U.S.–based Institute of Electrical and Electronics Engineers.
That report said many nanoproducts may remain profitable despite their high energy cost only because of enormous government subsidies to the nanotech industry—$1.6 billion from the U.S. government last year.
But despite all this, regulation of nanotech remains glacially slow. The European Parliament voted nearly unanimously to recommend that nanoproducts be banned from food in 2009. But the European Commission rejected that recommendation last year, agreeing only that it may require labels on food containing nanomaterials. It will also require labels on cosmetics containing some nanoingredients starting in 2014.
Canada and the U.S. have yet to go even that far. At Health Canada, which regulates nanotechnology, a web page dealing with nanoproducts hasn’t been amended in four years and contains outdated information.
Health Canada spokesman Stéphane Shank did not return calls.
They used to say small is beautiful. But that was before small got scary. – Straight.com
NO MEANS NO, YES MEANS NO TOO
So yeah, that’s it for now, and if you think this is not enough to prove much, you can’t be more wrong, you’re probably bathing in dangerous or lethal nanotech as you read this, but feel free to return to this link in the coming days and weeks, I will be adding more evidence as I dig it out. I have about 100 leads there, it’s going to be a long process, friends!
To be continued? Our work and existence, as media and people, is funded solely by our most generous supporters. But we’re not really covering our costs so far, and we’re in dire needs to upgrade our equipment, especially for video production. Help SILVIEW.media survive and grow, please donate here, anything helps. Thank you!
! Articles can always be subject of later editing as a way of perfecting them
Graphene is the new asbestos. Plus injectable and mandatory. The rest Of the graphene oxide story is here, if you need more background, this post is a result of that investigation
NOTE: A needed clarification solicited by some readers: Yes, we knew of GRAPHENE COATING on masks in May, as seen below, which is horrible enough, even more so since not many followed Canada’s example in banning it. What this article brings new is a confirmation for GRAPHENE OXYDE, which is not very different in properties and health impact, but seems to be specific to these mRNA jabs, and so we complete the new revelations on graphene oxide and vaccines from La Quinta Columna.
In December 2019, a novel coronavirus (SARS-CoV-2) was first detected in Wuhan, in China’s Hubei province. On 11 March 2020, the World Health Organization (WHO) acknowledged and characterized the condition as a pandemic owing to the rapid spread of the virus across the globe infecting millions of individuals. Scientists are fighting tirelessly to find out ways to curb the spread of the virus and eradicate it.
SARS-CoV-2 is regarded as highly contagious and spreads rapidly through person-to-person contact. When an infected person sneezes or coughs, their respiratory droplets can easily infect a healthy individual. Besides enforcing social distancing, common citizens are encouraged to wear face masks to prevent droplets from getting through the air and infecting others.
Despite the efficiency of N95, a respiratory protective device, to filter out 95% of particles (≥0.3 μm), surgical facemasks are single-use, expensive, and often ill-fitting, which significantly reduces their effectiveness. Nanoscience researchers have envisioned a new respirator facemask that would be highly efficient, recyclable, customizable, reusable, and have antimicrobial and antiviral properties.
Nanotechnology in the Production of Surgical Masks
Nanoparticles are extensively used for their novel properties in various fields of science and technology.
In the current pandemic situation, scientists have adopted this technology to produce the most efficient masks. Researchers have used a novel electrospinning technology in the production of nanofiber membranes. These nanofiber membranes are designed to have various regulating properties such as fiber diameter, porosity ratio, and many other microstructural factors that could be utilized to produce high-quality face masks. Researchers in Egypt have developed face masks using nanotechnology with the help of the following components:
Polylactic acid
This transparent polymeric material is derived from starch and carbohydrate. It has high elasticity and is biodegradable. Researchers found that electrospun polylactic acid membranes possess high prospects for the production of filters efficient in the isolation of environmental pollutants, such as atmospheric aerosol and submicron particulates dispersed in the air.
Despite its various biomedical applications (implant prostheses, catheters, tissue scaffolds, etc.), these polylactic membranes are brittle. Therefore, applying frequent pressure during their usage could produce cracks that would make them permeable to viral particles. However, this mechanical drawback can be fixed using other supportive nanoparticles that could impart mechanical strength, antimicrobial and antiviral properties, which are important in making face masks effective in the current pandemic situation.
Copper oxide nanoparticles
These nanoparticles have many biomedical applications, for example, infection control, as they can inhibit the growth of microorganisms (fungi, bacteria) and viruses. It has also been reported that SARS-CoV-2 has lower stability on the metallic copper surface than other materials, such as plastic or stainless steel. Therefore, the integration of copper oxide nanoparticles in a nanofibrous polymeric filtration system would significantly prevent microbial adherence onto the membrane.
Graphene oxide nanoparticles
These nanoparticles possess exceptional properties, such as high toughness, superior electrical conductivity, biocompatibility, and antiviral and antibacterial activity. Such nanoparticles could be utilized in the production of masks.
Cellulose acetate
This is a semi-synthetic polymer derived from cellulose. It is used in ultrafiltration because of its biocompatibility, high selectivity, and low cost. It is also used in protective clothing, tissue engineering, and nanocomposite applications.
With the help of the aforesaid components, researchers in Egypt have designed a novel respirator filter mask against SARS-CoV-2. This mask is based on a disposable filter piece composed of the unwoven nanofibers comprising multilayers of a) copper oxide nanoparticles, graphene oxide nanoparticles, and polylactic acid, or b) copper oxide nanoparticles, graphene oxide nanoparticles, and cellulose acetate, with the help of electrospun technology and high-power ultrasonication. These facemasks are reusable, i.e., washable in water and could be sterilized using an ultraviolet lamp (λ = 250 nm).
SOURCE WORKING TO GET CONFIRMATION FROM THESE GUYS TOOSOURCE
Graphene-coated face masks: COVID-19 miracle or another health risk?
As a COVID-19 and medical device researcher, I understand the importance of face masks to prevent the spread of the coronavirus. So I am intrigued that some mask manufacturers have begun adding graphene coatings to their face masks to inactivate the virus. Many viruses, fungi and bacteria are incapacitated by graphene in laboratory studies, including feline coronavirus.
Because SARS CoV-2, the coronavirus that causes COVID-19, can survive on the outer surface of a face mask for days, people who touch the mask and then rub their eyes, nose, or mouth may risk getting COVID-19. So these manufacturers seem to be reasoning that graphene coatings on their reusable and disposable face masks will add some anti-virus protection. But in March, the Quebec provincial government removed these masks from schools and daycare centers after Health Canada, Canada’s national public health agency, warned that inhaling the graphene could lead to asbestos-like lung damage.
Is this move warranted by the facts, or an over-reaction? To answer that question, it can help to know more about what graphene is, how it kills microbes, including the SARS-COV-2 virus, and what scientists know so far about the potential health impacts of breathing in graphene.
How does graphene damage viruses, bacteria and human cells?
Graphene is a thin but strong and conductive two-dimensional sheet of carbon atoms. There are three ways that it can help prevent the spread of microbes:
Microscopic graphene particles have sharp edges that mechanically damage viruses and cells as they pass by them.
Graphene is negatively charged with highly mobile electrons that electrostaticly trap and inactivate some viruses and cells.
Dr Joe Schwarcz explains why Canada banned graphene masks. Doesn’t say why other countries didn’t. When two governments have opposing views on a poison, one is criminally wrong and someone has to pay.
Why graphene may be linked to lung injury
Researchers have been studying the potential negative impacts of inhaling microscopic graphene on mammals. In one 2016 experiment, mice with graphene placed in their lungs experienced localized lung tissue damage, inflammation, formation of granulomas (where the body tries to wall off the graphene), and persistent lung injury, similar to what occurs when humans inhale asbestos. A different study from 2013 found that when human cells were bound to graphene, the cells were damaged.
In order to mimic human lungs, scientists have developed biological models designed to simulate the impact of high concentration aerosolized graphene—graphene in the form of a fine spray or suspension in air—on industrial workers. One such study published in March 2020 found that a lifetime of industrial exposure to graphene induced inflammation and weakened the simulated lungs’ protective barrier.
It’s important to note that these models are not perfect options for studying the dramatically lower levels of graphene inhaled from a face mask, but researchers have used them in the past to learn more about these sorts of exposures. A study from 2016 found that a small portion of aerosolized graphene nanoparticles could move down a simulated mouth and nose passages and penetrate into the lungs. A 2018 study found that brief exposure to a lower amount of aerosolized graphene did not notably damage lung cells in a model.
From my perspective as a researcher, this trio of findings suggest that a little bit of graphene in the lungs is likely OK, but a lot is dangerous.
Although it might seem obvious to compare inhaling graphene to the well-known harms of breathing in asbestos, the two substances behave differently in one key way. The body’s natural system for disposing of foreign particles cannot remove asbestos, which is why long-term exposure to asbestos can lead to the cancer mesothelioma. But in studies using mouse models to measure the impact of high dose lung exposure to graphene, the body’s natural disposal system does remove the graphene, although it occurs very slowly over 30 to 90 days.
The findings of these studies shed light on the possible health impacts of breathing in microscopic graphene in either small or large doses. However, these models don’t reflect the full complexity of human experiences. So the strength of the evidence about either the benefit of wearing a graphene mask, or the harm of inhaling microscopic graphene as a result of wearing it, is very weak.
No obvious benefit but theoretical risk
Graphene is an intriguing scientific advance that may speed up the demise of COVID-19 virus particles on a face mask. In exchange for this unknown level of added protection, there is a theoretical risk that breathing through a graphene-coated mask will liberate graphene particles that make it through the other filter layers on the mask and penetrate into the lung. If inhaled, the body may not remove these particles rapidly enough to prevent lung damage.
The health department in Quebec is erring on the side of caution. Children are at very low risk of COVID-19 mortality or hospitalization, although they may infect others, so the theoretical risk from graphene exposure is too great. However, adults at high immediate risk of harm from contracting COVID-19 may choose to accept a small theoretical risk of long-term lung damage from graphene in exchange for these potential benefits.
To be continued? Our work and existence, as media and people, is funded solely by our most generous supporters. But we’re not really covering our costs so far, and we’re in dire needs to upgrade our equipment, especially for video production. Help SILVIEW.media survive and grow, please donate here, anything helps. Thank you!
! Articles can always be subject of later editing as a way of perfecting them
An editorial that stands by itself and speaks volumes for many of the incredible facts I’ve revealed in my own editorials. I don’t endorse all this, I just chew the meat on the bones. Published in a journal called Expert Opinion on Drug Delivery
Manipulative magnetic nanomedicine: the future of COVID-19 pandemic/endemic therapy
By Ajeet Kaushik, Pages 531-534 | Received 06 Nov 2020, Accepted 03 Dec 2020, Published online: 14 Dec 2020
1. Introduction: COVID-19 pandemic or endemic as health emergency
Since the Spanish flu outbreak (1918), many pandemics and/or endemics related to a viral infection such as H1N1, H5N1, human immunodeficiency virus (HIV), Ebola, Zika, and coronavirus have surprised mankind time-to-time due to their sudden appearance, severe adverse health effect, loss of lives, socio-economic burden, and a damaged economy. Such deadly infectious viruses originated from natural reservoirs and then infect humans via spillover mechanism. During infection progression, viruses affect the human biological system and become a part of the host genome and then make structural changes in its structure to survive or infect longer. These infections can cause permanent disorders, may be death, if a patient is immunocompromised and could not fight against virus life-cycle associated pathways and viral infection progression.
One such pandemic and/or endemic is the recent COVID-19 infection associated with new server acute respiratory syndrome coronavirus (SARS-CoV-2), investigated by Chinese clinicians in Dec 2019. Chinese health agencies noticed a rapid increment in seasonal flu cases, and this emerged as a very serious health issue due to the ineffectiveness of prescribed therapies [1,2]. Systematic investigations conducted on this infectious disease by experts confirmed and claimed that SARS-CoV-2 virus infection is dramatically affecting the respiratory system of every age patient via affecting their lung function. Although SARS-CoV-2 virus protein exhibited 70% to 80% genomic profile like SARS-CoV-1 (2002 outbreak) and middle east respiratory syndrome (2012 outbreak), but its viral infection mechanism, pathogenesis, mortality per cent, and other risks are different, unknown, and serious than SARS and MERS [2]. Considering the severity of COVID-19 infection and variation in SARS-CoV-2 virus strains, this outbreak was first declared as an international health emergency; then, a pandemic due to global spread [2], and now experts are projecting this as an endemic due to post-infection effects and possibilities of reoccurrence like HIV [3]. This infection is emerging very challenging due to 1) human-to-human transmission via aerosolization, 2) ability to affect lung rapidly because of easy binding between Spike (S1) protein of SARS-COV-2 virus and host cell membrane receptors like angiotensin-converting enzyme 2 (ACE-2) and TMPRSS-2 protein, this makes virus replication easy [4].
A successful COVID-19 infection management is not the only issue to deal with the respiratory system as it affects lung function. But the SARS-CoV-2 virus infection also severely affects other important body organs including the heart, liver, eye, gut, and brain as well. This is the reason that recovery of a COVID-19 infected patient is slow and sometimes the patient exhibits permanent disorder in biological function due to weak organs and organ function [2]. Such scenarios have been investigated in asymptomatic patients as well. Keeping complete COVID-19 outbreak into consideration, health agencies were focused on 1) preparation and execution of safety guidelines, 2) exploring virus structure, genomic profiles, variability, and generate bioinformatics to understand pathogenesis, 3) developing rapid diagnostic kits, 4) optimizing available therapies, alone or in combination, 5) exploring methodologies to prevent SARS-CoV-2 transmission, 6) exploring novel therapeutics, 7) exploring aspects of therapeutic delivery at disease location, and 8) exploring combinational aspects of nanobiotechnology to support rapid testing, trapping of SARS-CoV-2, and delivery of therapeutics for not only to eradicate SARS-CoV-2 but provide long-term immunity for COVID-19 infected patient [4–6].
Based on the outcomes of big data analytics based on artificial intelligence (AI), it is suggested that recognition and eradication of the SARS-CoV-2 virus may be a time-taking procedure. Thus, all the focus is toward rapid infection diagnostics and viral infection management using state-of-the-art technologies, for example, 1) promoting physical distance and using of a mask to avoid virus transmission, 2) developing AI and internet-of-medical-things (IoMT) based strategies for rapid testing, tracking of patients, big data analytics, bioinformatics generation, developing a novel sensor for early-stage SARS-CoV-2 detection [2,5,7], and novel therapeutics and successful delivery using nanobiotechnology approach [8], the main focus of this editorial.
2. Manipulative magnetic nanomedicine: the future of COVID-19 therapy
Nanobiotechnology is emerging very promising to investigate novel methodologies for managing COVID-19 pandemic/endemic successfully [2,5]. In this direction, experts have explored the opto-electro-magnetic nanosystem to detect the SARS-CoV-2 virus using a biosensing approach. Such optical, electrical, or magnetic biosensors function based on geno-sensing and immune-sensing has detected the SARS-CoV-2 virus selectively at a very low level [7,8]. These efficient-miniaturized biosensors can be operated using a smartphone and promoted for clinical application for early-stage diagnostics of COVID-19 infection. The successful integration of these SARS-CoV-2 virus sensors with AI and IoMT enables virus detection at point-of-location and sharing of bioinformatics with the medical center at the same time for timely therapeutics decision. This approach is also useful for tracking tasks and managing COVID-19 infection according to patient infection profiling. To avoid human-to-human SARS-CoV-2 virus transmission, experts have developed stimuli-responsive nanotechnology enable which can not only trap aerosol of virus size but can eradicate viruses on applying external stimulation for example nanoenable photo-sensitive virus degradation. Various types of clothes containing nanoparticles have demonstrated SARS-CoV-2 virus trapping and eradication successfully [2,9]. However, significant attention is required to increase the production and distribution of these masks for public use.
Besides, the contribution of biotech-pharma companies is also of high significance in terms of investigating novel therapeutic agents of higher efficacy with least/acceptable adverse effects. Though the SARS-CoV-2 virus is new and has exhibited strain variation which is making treatment optimization challenging. But biotechnology experts are analyzing every aspect of bioinformatics to design and develop an effective therapy based on novel anti-viral agents, CRISPR-Cas, antibodies, and vaccines5. Another approach to manage COVID-19 infection is to introduce or boost immunity through nutrition, for example, nutraceuticals have acted as inhibitors to prevent binding between SARS-CoV-2 virus and ACE-2 enzyme [2,8].
Investigating a therapeutic agent against the SARS-CoV-2 virus infection seems possible now but the delivery of these agents is still a remaining challenge because this virus may have numerous reservoirs over the time. It is also demonstrated that COVID-19 infection patients may temporarily or permanently have immunocompromised biological systems. Such-related adverse effects include risk of cardiac arrest, vision issues, weak respiratory system, neurological disorders (one of the serious issues because SARS-CoV-2 virus crosses the blood-brain barrier), etc. Therefore, a single therapeutic agent designed against the SARS-CoV-2 virus may not be enough to treat COVID-19 infected patients completely [1,8].
Thus, a manipulative therapy, a combination of optimized therapeutic agents, consisting of an anti-SARS-CoV-2 virus agent and immune-supportive agents will require to be optimized based on the patient infection profiling. Experts have thought about it and raised/dealing the following concerns 1) drug-to-drug interaction, 2) delivery of drug/drugs at the targeted site, 3) control over the release of drug/drugs from a therapeutic formulation, and 4) immune-supporting long-acting therapies. These tasks are challenging but needed to be managed; therefore, exploring aspects of nanomedicine could be a promising approach to develop novel therapies to manage COVID-19 infection and support the immune system along with SARS-CoV-2 virus affected organs [8].
Nanomedicine (10 to 200 nm) is a therapeutic cargo designed using an appropriate drug nanocarrier and a therapeutic agent [9–15]. Nowadays magnetic nanomedicine has performed to manage viral infection at various reservoirs even in the brain because nanomedicine is capable to cross any barriers in the body via adopting the following approaches 1) functionalization of nanomedicine with barriers specific receptors, 2) applying external stimulation like ultrasound, and 3) noninvasive guided approach like magnetically guided drug delivery system [10–12].
Besides drug delivery, magnetic nanomedicine could be formulated to deliver multiple drugs at a targeted site to achieve desired therapeutic performance due to 1) control over the release by applying external stimulation like an ac-magnetic field, 2) formulating a magnetic cargo to load multiple drugs without drug-to-drug interaction, for example, layer-by-layer (LBL) approach, and 3) the sequence of drug release can be tuned and planned according to a stage/requirement of disease condition [13–15]. The performance of such nanomedicine mainly depends on the selection of a multi-functional stimuli-response drug nanocarrier such as magneto-electric nanoparticles (MENPs) [12], opto-magnetic, opto-electromagnetic, magneto-LBL, magneto-liposome, and magneto-plasmonics nanosystem. These advanced nanomedicines not only deliver the drug/drug but also help in the recognition of drug distribution and disease progression.
Combining above mentioned salient features, manipulative magnetic nanomedicine (MMN) as one of the potential future therapy wherein control over delivery and performance if required. Such MMN has the capabilities to recognize and eradicate the SARS-CoV-2 virus to manage COVID-19 infection and symptoms. Besides, due to the flexibility of using the therapeutic agent of choice, these manipulative nanomedicines can be designed and developed as long-acting therapy for COVID-19 infection where anti-virus and immune-supportive agents can stay longer in the body without causing any side-effects. Such personalized MMN (Figure 1) is an urgently required therapy and its development should be the focus of future research with the following aims
Figure 1. Systematic illustration of manipulative nanomedicine projected as future COVID-19 pandemic/endemic therapyDisplay full size
Exploring stimuli-responsive magnetic nanosystems for on-demand-controlled delivery and release.
Image-guided therapy to recognize the delivery site and confirm drug release.
A magnetically guided approach to delivering drugs across the barriers like the gut, BBB, etc.
Magneto-LBL/liposomal approach to delivering multiple drugs to avoid drug-to-drug interaction and control over the drug release sequence. For example, an anti-virus drug should be released first then an immune-protective agent.
The MMN can be customized according to patient disease profile and medical history, for example, selection of anti-SARS-CoV-2 virus agent (antibody, ARV, CRISPR-Cas, etc.,) based on patient genomic profiling.
The MMN can also be customized as long-acting therapeutics that allows drug-releasing for a longer time (2–3 months), as must require therapy to manage post-COVID-19 infection effects.
The MMN can be explored as personalized precision therapy.
3. Expert opinion
Based on the experiences of developing MMN to eradicate neuroHIV/AIDS, under a project of getting into the brain, using MENPs as a drug nanocarrier, magnetically guided drug delivery, and ac-magnetic field stimulation dependent controlled drug release, my team and me believes that MMN can be a future therapy against COVID-19 infection pandemic/or endemic. As it is also known that the SARS-CoV-2 virus infection is a combination of several diseases and symptoms. During the infection treatment, even after the hospital discharge, the patient may have several diseases at the same time for a longer time. Such-complicated medical conditions are not easy to deal with using conventional antiviral drugs. Thus, experts feel the demand for a new therapy that can handle multiple tasks at the same time. Keeping advancements and potentials into consideration, manipulative nanomedicine can be one of the potential COVID-19 infection therapies.
Some of the advancements in this field has been reported, for example, micro-needle-based vaccine delivery to manage COVID-19 infection. Early outcomes are exciting, but a lot must be done in terms of animal model-based trials, and followed up with FDA approval, needed prior to suggest clinical implication. To promote MNM against COVID-19 successfully, a public-private involvement-based significant research needed to be conducted in this field to create a path from a lab (in-vitro) to in-vivo (appropriate animal model) to risk assessments to clinical trials to risk assessment to human trial to risk assessment to FDA approval for public utilization. In the process of developing an anti-COVID-19 infection therapy, careful and critical safety-related risk assessments will be a crucial factor to decide progression step-by-step. This introducing AI will be a good choice to gather bioinformatics, perform big data analysis, avoid unnecessary hit-&-trial approaches, establish a relation with a biological and pathological parameter, and projection of a potential approach. Besides AI, it is also suggested to design several projects focused on every aspect of pre/post-SARS-CoV-2 virus infection, and based on assessments and analytics a potential drug nanocarrier and therapeutics agents should be selected. Developing such an approach is a multidisciplinary research approach and experts of various expertise are needed to work on the same platform to investigate MMN to combat against SARS-CoV-2 virus infection. Projecting the above mention as a necessity, this editorial is a call to experts to join hands for investigating and promoting MMN as a potential future COVID-19 pandemic/endemic therapy. I believe that the MMN approach will be in more demand as new therapeutic agents, such BNT162b2, and mRNA1273 [16], vaccine as will be investigated over the time.
References
From author’s references, I want to highlight this study which shows that magnetism is also used to cross the Brain Blood Barrier -Silview
Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection
CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (hμglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60 Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent hμglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS.
Yamamoto V, Bolanos JF, Fiallos J, et al. COVID-19: review of a 21st century pandemic from etiology to neuro-psychiatric implications. J Alzheimers Dis. 2020;77(2):459–504. . [Crossref], [PubMed], [Web of Science ®], [Google Scholar]•• Article explains COVID-19 outbreak, SARS-CoV-2 virus, and state-of-art approach for diagnostics, treatment, and post-infection management.
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When I first heard of blood clots in vaccinated people, I instantly recalled of a similar problem occurring while the mRNA platform was in study for a cancer therapy, by Moderna, I think, prior to Covid. I couldn’t find that piece of information again, but during the research I discovered something even more revealing.
Blood clots in subjects of Covid gene therapies are very likely caused by defective coatings in magnetic particles used for magnetofection, which leads to cell-clogging.
Silviu “Silview” Costinescu
It has been more than plausibly theorized that the explanation for the magnetism in vaxxers is magnetofection, a method of transfection using magnetic fields.
Magnetofection is a very effective way of transfecting plasmid DNA into a variety of primary cells including primary neurons which are known to be notoriously difficult to transfect and very sensitive to toxicity.
For coincidence theorists, let me just add that the inventor of transfection is one of mRNA jabs inventors, Dr. Robert Malone, who has warned FDA on the dangers of these technologies, according to himself.
Scientifically trained at UC Davis, UC San Diego, and at the Salk Institute Molecular Biology and Virology laboratories, Dr. Robert Malone is an internationally recognized scientist (virology, immunology, molecular biology) and is known as one of the original inventors of mRNA vaccination and DNA Vaccination. His discoveries in mRNA non viral delivery systems are considered the key to the current COVID-19 vaccine strategies. Dr. Malone holds numerous fundamental domestic and foreign patents in the fields of gene delivery, delivery formulations, and vaccines. Dr. Malone has close to 100 peer-reviewed publications and published abstracts and has over 11,477 citations of his peer reviewed publications, as verified by Google Scholar. His google scholar ranking is “outstanding” for impact factors. He has been an invited speaker at over 50 conferences, has chaired numerous conferences and he has sat on or served as chairperson on numerous NIAID and DoD study sections.
Magnetofection basically involves attaching DNA onto a magnetic nanoparticle coated with a cationic polymer like polyethylenimine (PEI) [254,255]. The magnetic nanoparticles are generally made up of a biodegradable substance like iron oxide, and its coating onto the polymeric particle is done by salt-induced colloidal aggregation. These prepared nanoparticles are then localized in the target organ by the application of an external magnetic field, which allows the delivery of attached DNA to the target organ, as shown in Figure 3.5. This method also increases the uptake of DNA into target cells as the contact time between the target organ and magnetic nanoparticles increases. In addition, the magnetic field pulls the magnetic nanoparticles into the target cells, which also helps to increase the uptake of DNA [256,257]. In addition, the standard transfection using viral or nonviral vectors is also increased by the magnetofection.
This is a more powerful method of controlled and targeted delivery for gene therapies, in layman terms.
The problem with it is that it’s been proven to be very dangerous for lab animals and it’s not authorized for human use.
From Dr. Jane Ruby m as well as from Pfizer and Moderna we find out how these particles are packaged into the injectable concocts:
“Stew Peters interviews Dr Jane Ruby who confirms the magnetic effects that Covid vaxxed people have experienced. She says it is a deliberately made substance added to the vaccines. This shows criminal intent. It was added because it is an aggressive delivery system to get it into EVERY cell of your body. The process is called ‘Magnetofection’ and is available in scientific literature such as Pubmed. It concentrates the mRNA into people’s cells and forces your body to make these synthetic mRNA instructions even in places where they shouldn’t be located within the body.
It is a ‘forced delivery system’ and is called by the acronym of SPIONS – Supramagnetic Iron Oxide Nanoparticles. These particles use a lipid nanoparticle envelope to gain entry into the cells. It is done this way to protect mRNA because mRNA is easily degraded and this is also why the Pfizer vaccines are refrigerated at -70 degrees Fahrenheit as another form of protection.
There is a German company on the internet called ‘Chemicell’ which sells different chemicals which can make these magnetic fields around your molecules. You can buy 200 microgram vials of their product called, ‘Polymag’. These are developed and sold for research purposes only and are not to be used for human diagnostic or as a component of any drug intended for humans.
However at least Pfizer and Moderna are using this substance in their vaccines. Therefore it is vital that anyone thinking of taking a shot, obtain a full ingredient list to have full informed consent and to postpone getting the Covid Jab, as each day brings further information into the public domain. Dr Ruby is asked if this was deliberate by the manufacturers and answers that this substance doesn’t occur naturally. It had to be added into the vaccine.
Many have spoken about the Polyethelene Glycol or PEG which enables the vaccines to get through water based cell membranes as this is lipophilic – attracted to fats – but there are other places in the body where ‘God and Nature’ hadn’t intended these substances to be, but by using this delivery system of supra nanoparticles, you are creating a super delivery system which forces these substances into areas where they are not meant to be.”
. 2019 Nov;13(9):1197-1209. doi: 10.1080/17435390.2019.1650969. Epub 2019 Aug 22.
Superparamagnetic iron oxide nanoparticles (SPIONs) modulate hERG ion channel activity
Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as diagnostic agents in magnetic resonance imaging (MRI), for drug delivery vehicles and in hyperthermia treatment of tumors.
Although the potential benefits of SPIONs are considerable, there is a distinct need to identify any potential cellular damage associated with their use.
Since human ether à go-go-related gene (hERG) channel, a protein involved in the repolarization phase of cardiac action potential, is considered one of the main targets in the drug discovery process, we decided to evaluate the effects of SPIONs on hERG channel activity and to determine whether the oxidation state, the dimensions and the coating of nanoparticles (NPs) can influence the interaction with hERG channel.
Using patch clamp recordings, we found that SPIONs inhibit hERG current and this effect depends on the coating of NPs. In particular, SPIONs with covalent coating aminopropylphosphonic acid (APPA) have a milder effect on hERG activity. We observed that the time-course of hERG channel modulation by SPIONs is biphasic, with a transient increase (∼20% of the amplitude) occurring within the first 1-3 min of perfusion of NPs, followed by a slower inhibition. Moreover, in the presence of SPIONs, deactivation kinetics accelerated and the activation and inactivation I-V curves were right-shifted, similarly to the effect described for the binding of other divalent metal ions (e.g. Cd2+ and Zn2+).
Finally, our data show that a bigger size and the complete oxidation of SPIONs can significantly decrease hERG channel inhibition.
Taken together, these results support the view that Fe2+ ions released from magnetite NPs may represent a cardiac risk factor, since they alter hERG gating and these alterations could compromise the cardiac action potential.
MIT SAYS IT’S NOT JUST SPIONS, BUT ALSO LIONS:
HDT Bio, the biotechnology company in Seattle, has an alternative solution. Working with Deborah Fuller, a microbiologist at the University of Washington, it’s pioneering a different kind of protective bubble for the mRNAs. If it works, it would mean that an mRNA vaccine for covid-19 could be stable in a regular fridge for at least a month, or at room temperature for up to three weeks.
Their method: instead of encasing the mRNA in a lipid nanoparticle, they’ve engineered molecules called lipid inorganic nanoparticles, or LIONs. The inorganic portion of the LION is a positively charged metal particle—so far they’ve been using iron oxide. The positively charged metal would bind to the negatively charged mRNA, which wraps around the LION. The resulting particle is solid, which creates more stability and reduces the reliance on refrigeration.
A real-world study by the CDC backs up the clinical trial data from both mRNA vaccines—although the rise of the UK variant in the US is a cloud on the horizon.
“The cold chain has always been an issue for [the] distribution of vaccines, and it’s only magnified in a pandemic.”
Deborah Fuller
HDT Bio initially developed LIONs to treat liver cancer and tumors in the head and neck, but when the pandemic hit, they pivoted to trying the particles with mRNA vaccines. Early preclinical trials in nonhuman primates showed that the LION, combined with an mRNA vaccine for covid-19, worked as they’d hoped.
Carter of HDT Bio says that in an ideal situation, LIONs could be sent to clinics worldwide in advance, to be stored at room temperature or in a regular refrigerator, before being mixed into vaccine vials at clinics. Alternatively, the two could be premixed at a manufacturing facility. Either way, this method would make doses stable for at least a month in a regular refrigerator.
Fuller says that some scientists have criticized the need for two vials—one for the LION and another for mRNA before they’re mixed together. “But I think the advantages of having an effective product more amenable to worldwide distribution outweighs those negatives,” she says.
HDT Bio is applying for permission to start human clinical trials in the US and is looking to start clinical trials in India this spring. In the US, it faces some unique challenges in FDA regulation, since the LION particles would be considered a drug separate from the vaccine. Regulators in Brazil, China, South Africa, and India—where HDT Bio is hoping to launch its product—don’t consider the LION a drug because it isn’t the active component, says Carter, meaning that there would be one less layer of regulation than in the US.
For now, it’s still very much an early-stage technology, says Michael Mitchell, a bioengineer at the University of Pennsylvania who works on drug delivery systems. He stresses that more research should reveal whether the iron oxide causes any side effects. – MIT Technology Review
Now here’s the bombshell:
This is no secret to experts, but it’s been revealed to me in the video presentation below, made in 2017 by reputed Prof Diana Borca, from Rensselaer Polytechnic Institute, who uses magnetic nanoparticles to treat diseases. In order to get the magnetic nanoparticles into the right places, scientists like Diana have to figure out what kind of coating the nanoparticles need. Coatings help the nanoparticles get to the cells they want to treat without hurting the healthy cells. And if the coating of the magnetic particles breaks, the result is “CLOGGING”, as Borca explains below. Which can translate as clotting, if in blood. Who knows what they lead to when in other organs, strokes maybe?
So I think the only thing we’re missing from the puzzle is official hard evidence that they used magnetofection or magnetogentic methods.
But if it walks like a duck and quacks like a duck, only the government needs government papers to confirm it’s a duck
What each and every one of you can do until we find that evidence?
On screens we’re sound. Please help with the statistical and empirical tests!
Please help finding out if there’s a strong data and empirical correlation between blood clots and magnetism. Anyone you know that has been jabbed and experienced blood clots, heart or circulatory problems needs to take the magnet challenge right now! A strong enough correlation indicates causation. If you make such a test, please reach us on our socials and communicate the result, whether positive or negative! Also VAERS is exploding with reports of magnetism, please help analyzing the data to see if it pairs with clotting. Thank you!
Also food for thought: isn’t this also related to the problems these GMO dupes experience during air-travel? I’ll investigate this in a soon coming report.
This chapter highlighted magnetofection, magnetic patterning of cells, and construction of 3D tissue-like structures. Among them, Mag-TE for constructing 3D structures has been extensively studied, and various kinds of other tissues such as retinal pigment epithelial cell sheets,102 MSC sheets,44 and cardiomyocyte sheets,46 have been already generated. Tubular structures consisting of heterotypic layers of endothelial cells, smooth muscle cells, and fibroblasts have also been created.43 In this approach, magnetically labeled cells formed a cell sheet onto which a cylindrical magnet was rolled, which was removed after a tubular structure was formed. If these processes can be scaled up, there is great potential for these techniques in the treatment of a variety of diseases and defects.
In the translational research, toxicology of functional magnetite nanoparticles is an important issue. The main requisite for a cell-labeling technique is to preserve the normal cell behavior. As for biocompatibility of MCLs, no toxic effects against proliferation of several cell types were observed within the range of magnetite concentrations tested (e.g., human keratinocytes,63 < 50 pg-magnetite/cell; HUVECs,41 HAECs,42 human dermal fibroblasts,41 human smooth muscle cells,43 mouse fibroblast cells,43 canine urothelial cells,43 human MSCs,44 and rat MSCs45 < 100 pg/cell). Moreover, MCLs did not compromise MSC differentiation44,45 or electrical connections of cardiomyocytes.46 In addition, an in vivo toxicity of magnetite nanoparticles has been extensively studied. As an MRI contrast agent, ResovistR was first applied clinically for detecting liver cancer, since ResovistR is taken up rapidly by the reticuloendothelial system such as Kupffer cells of the liver compared with the uptake by cancer cells of the liver. In a preliminary study,103 the authors investigated the toxicity of systemically administered MCLs (90 mg, i.p.) in mice; none of the 10 mice injected with MCLs died during the study. Transient accumulation of magnetite was observed in the liver and spleen of the mice, but the magnetite nanoparticles had been cleared from circulation by hepatic Kupffer cells in the spleen by the 10th day after administration.103
In conclusion, magnetic nanoparticles have been developed into “functional” magnetite nanoparticles which are highly promising tools for a wide spectrum of applications in tissue engineering. The proven lack of toxicity of the functional magnetite nanoparticles is expected to provide exciting tools in the near future for clinical tissue engineering and regenerative medicine.View chapter
One of the pioneers using magnetofection for in vitro applications was Lin et al.91 There are various cationic magnetic nanoparticles types that have the capacity to bind nucleotidic material on their surface. With this method, the magnetic nanoparticles are concentrated in the target cells by the influence of an external magnetic field (EMF). Normally, the internalization is accomplished by endocytosis or pinocytosis, so the membrane architecture stays intact. This is an advantage over other physical transfection methods. Other advantages are the low vector dose needed to reach saturation yield and the short incubation time needed to achieve high transfection efficiency. Moreover, with the application of an EMF, cells transfected with magnetic nanoparticles can be used to target the region of interest in vivo.
2.2.1.1 Iron Oxide Nanoparticles
The magnetic nanoparticles most used in magnetofection include the iron oxide nanoparticles (IONPs). IONPs are biodegradable and not cytotoxic and can be easily functionalized with PEI, PEG, or PLL. Poly-l-lysine-modified iron oxide nanoparticles (IONP–PLL) are good candidates as DNA and microRNA (miRNA) vectors because they bind and protect nucleic acids and showed high transfection efficiency in vitro. In addition, they are highly biocompatible in vivo.
Chen et al.92 used human vascular endothelial growth factor siRNA bound to superparamagnetic iron oxide nanoparticles (SPIONs) and it was capable of hepatocellular carcinoma growth inhibition in nude mice. Moreover, Li et al.93 demonstrated that the intravenous injection of IONP–PLL carrying NM23-H1 (a tumor suppressor gene) plasmid DNA significantly extended the survival time of an experimental pulmonary metastasis mouse model.
Another advantage of this kind of nanoparticles is that they can be used as MRI agents. Chen et al.94 bound siRNA to PEG-PEI SPIONs together to a gastric cancer-associated CD44v6 single-chain variable fragment. This bound permitted both cancer cell’s transfection and their visualization by MRI.
But those complexes might be used for cell therapies as well. Schade et al.95 used iron oxide magnetic nanoparticles (MNPs) to bind miRNA and transfect human mesenchymal stem cells. As the binding between the MNPs and PEI took place via biotin-streptavidin conjugation, these particles cannot pass the nuclear barrier, so they are good candidates to deliver miRNA, as it exerts its function in the cytosol. They functionalized the surface nanoparticles with PEI and were able to obtain a better transfection than PEI 72 h after transfection. Moreover, they demonstrated that magnetic polyplexes provided a better long-term effect, also when included inside of the stem cells.View chapter
Another attempt to apply magnetic IONPs is the so-called magnetofection (MF) approach. Key factors enabling this method are IONPs that are coupled to vector DNA and guided by the influence of an external magnetic field. By this means, DNA can be transfected into cells of interest. One possibility to enable enhanced binding capabilities of the negatively charged DNA to magnetic IONP beads is the coating IONPs with a positively charged material such as polyethylenimine. The efficiency of the vectors has hence shown to increase up to several thousand times (Scherer et al., 2002). The above depicted engagement of IONPs in MF has shown to be universally applicable to viral and nonviral vectors. This is mostly because it is very rapid and simple. Furthermore, it is a very attractive approach since it yields saturation level transfection at low-dose in vitro (Krotz et al., 2003). Fernandes and Chari (2016) have demonstrated an approach delivering DNA minicircles (mcDNA) to neural stem cells (NSCs) by means of MF. DNA minicircles are small DNA vectors encoding essential gene expression components but devoid of a bacterial backbone, thereby reducing construct size versus conventional plasmids. This could be shown to be very beneficial for the use of genetically engineered NSC transplant populations in regenerative neurology. The aim was to improve the release of biomolecules in ex vivo gene therapy. It could be demonstrated that MF of DNA minicircles is very safe and provided for sustained gene expression for up to 4 weeks. It is described to have high potential as clinically translatable genetic modification strategy for cell therapy (Fernandes and Chari, 2016). The last in vitro application for magnetic nanoparticles to be presented in this chapter will be tissue repair.View chapter
Two methods rely on the application of a magnetic field for gene transfer. Magnetofection uses magnetic nanoparticles coated with DNA in presence of a magnetic field. The nucleic acid-nanoparticle complexes are driven toward and into the target cells by magnetic force application. Gene transfer is enhanced by magnetofection as DNA-loaded particles are guided and maintained in close contact with the target cells. Cellular uptake through endocytosis is thus increased as well. The process has been mainly applied to cultured cells and has been proven more efficient than other chemical methods in some cases.8 The second method is magnetoporation in which membrane permeability is increased, triggered by the applied magnetic field.9View chapter
For gene therapy applications, magnetic particles are generally used for increasing the transfection efficiencies of cultured cells, a technique known as magnetofection [91–104] in which magnetic particles and nucleic acids are mixed together and then added to the cell culture media. The nucleic acid-bound magnetic particles then move from the media to the cell surface upon the application of an external magnetic force, as shown in Figure 9.1. The principle advantage of this approach is the rapid sedimentation of the gene-therapeutic agent onto the target area, thereby reducing the time and dose of vector to achieve highly efficient transfection, with lower cell cytotoxicity.
In in vivo magentofection, the magnetic field is focused over the target site. This method has the potential not only to enhance transfection efficiency but also to target the therapeutic gene to a specific organ or site, as shown in Figure 9.2.
Generally, magnetic particles carrying therapeutic genes are injected intravenously. As the particles flow through the bloodstream, they are captured at the target site using very strong, high-gradient external magnets. Once they are captured, the magnetic particles carrying the therapeutic gene are taken up by the tissue, followed by release of the gene via enzymatic cleavage of cross-linked molecules or degradation of the polymer matrix. If DNA is embedded inside or within the coating material, the magnetic field must be applied to heat the particles and release the gene from the magnetic carrier [105].View chapter
In an attempt to address the transient damage caused by the invasive methods mentioned above (i.e., hydrodynamic injection and electroporation), magnetofection techniques have been introduced. This technique uses the physical method of a magnetic field to direct the deliver of genetic material to the desired target site. The concept involves attaching DNA to a magnetic nanoparticle usually consisting of a biodegradable substance such as iron oxide and coated with cationic polymer such as PEI (Mulens, Morales, & Barber, 2013). These magnetic nanoparticles are then targeted to the tissue through a magnetic field generated by an external magnet. The magnetic nanoparticles are pulled into the target cells increasing the uptake of DNA. This technique is noninvasive and can precisely target the genetic material to the desired site while increasing gene expression. The drawback to magnetofection is the need to formulate magnetic nanoparticles complexed with naked DNA, as well as the need for strong external magnets.View chapter
Stimulus-guided delivery is a non-invasive and convenient approach for clinical applications. Several methods in this category, including electroporation, ultrasound and magnetofection, have been used to deliver siRNAs to specific tissue sites. Owing to constraints associated with application of external stimuli under in vivo conditions, most such studies have been done in vitro. However, in vivo applications of stimulus-guided delivery of anticancer siRNAs are increasingly being reported.
Electroporation has been studied as a means for facilitating in vivo delivery of anticancer siRNAs. Notably, an electroporation method employing a new type of ‘plate and fork’ type electrode has been applied in vivo in mice (Takei et al., 2008). In this application, a chemically modified form of VEGF-specific siRNA in phosphate-buffered saline was intratumorally administered at three doses of 0.08, 0.17 and 0.33 mg/kg, or intravenously administered at a single dose of 6.6 mg/kg. Then, an electronic pulse was applied to a pair of plate and fork electrodes pre-inserted into PC-3-xenografted tumour tissues. Application of electroporation inhibited tumour growth to a similar degree after 0.17 mg/kg intratumoral and 6.6 mg/kg intravenous doses, in each case producing a 40-fold greater inhibitory effect than a local dose. Notably, the duration of the antitumour effect was maintained for 20 days after a single injection via the local or systemic route.
Magnetically guided in vivo siRNA delivery has been investigated using magnetic crystal-lipid nanostructures (Namiki et al., 2009). In this study, a magnetitenanocrystal was coated with oleic acid and a cationic lipid shell, and complexed to EGFR-specific siRNA. Following intravenous administration to mice, siRNA complexed to the magnetic core-encapsulated cationic lipid shell showed a rank order of tissue distribution of spleen followed by liver and lung. For in vivo magnetofection, titanium nitride-coated magnets were internally implanted under the skin peripheral to tumour lesions or were externally placed onto the skin. Mice were intravenously given a total of eight 0.3 mg/kg doses of siRNA complexed to cationic nanoshells administered every other day. Both internal and external applications of a magnetic field reduced tumour (MKN-74 or NUGC-4) volume by 50% compared with the control group 28 days after the initiation of treatment.
Ultrasound-guided siRNA delivery has also been used to increase the in vivo delivery of siRNAs. Ultrasound can produce cavitation, thereby resulting in transient disruptions in cell membranes within tissues (Vandenbroucke et al., 2008). Few studies have addressed the in vivo antitumour effects of ultrasound-guided anticancer siRNAs. To date, most such studies have evaluated the feasibility of the method using siRNAs specific for reporter genes, such as enhanced green fluorescent protein (Negishi et al., 2008). In this latter study, PEG-modified cationic lipid nanobubbles entrapping the ultrasound imaging gas perfluoropropane were complexed with enhanced green fluorescent protein-specific siRNA and intramuscularly administered at a dose of 0.15 mg/kg to mice transfected 1 day prior with enhanced green fluorescent protein-encoding plasmid DNA. Three days after siRNA injection and ultrasound application, fluorescent protein levels at the injection sites were reduced.
Although the feasibility of in vivo applications of stimulus-guided delivery of anticancer siRNA has been demonstrated and positive results have been reported, the ultimate success of these delivery methods may depend on the development of devices capable of providing a sufficient stimulus to tumour tissues deep within the body. Moreover, for in vivosystemic administration, delivery systems that carry both external stimulus-responsive agents and siRNA must meet more general requirements, such as in vivo stability, low toxicity and enhanced tumour tissue accumulation. With the concurrent progress in medical device bioengineering and siRNA delivery technologies, it can be expected that stimulus-guided strategies will be used in more diverse in vivo applications to facilitate anticancer siRNA delivery.View chapter
Various physical methods of gene delivery have been developed, and each one has its own merits and demerits. EP is particularly important for introducing DNA to superficial areas, but to deliver DNA to particular organs, surgery is required. To overcome this problem and to enhance the introduction of gene vectors into cells [254], the new means of physical gene delivery is magnetofection, which delivers DNA to the target organ, using the magnetic field. Magnetofection basically involves attaching DNA onto a magnetic nanoparticle coated with a cationic polymer like polyethylenimine (PEI) [254,255]. The magnetic nanoparticles are generally made up of a biodegradable substance like iron oxide, and its coating onto the polymeric particle is done by salt-induced colloidal aggregation. These prepared nanoparticles are then localized in the target organ by the application of an external magnetic field, which allows the delivery of attached DNA to the target organ, as shown in Figure 3.5. This method also increases the uptake of DNA into target cells as the contact time between the target organ and magnetic nanoparticles increases. In addition, the magnetic field pulls the magnetic nanoparticles into the target cells, which also helps to increase the uptake of DNA [256,257]. In addition, the standard transfection using viral or nonviral vectors is also increased by the magnetofection.
The magnetofection has some drawbacks: a particle size below 50 nm renders it not suitable for magnetic targeting and too large a particle size (more than 5 μm) retards the entry of magnetic nanoparticles inside the blood capillaries. The blood flow rate also affects the transfection efficacy of this method; for example, the flow rate of around 20 cm/s in the human aorta makes the transfection tricky. The external magnetic flux density and gradient decreases at a distance from the magnetic pole, which also affects the transfection efficacy.
Primary endothelial cells are effectively transfected by magnetofection [254,258]. In addition, magnetofection is effective for in vitro and in vivo delivery of DNA to target cells like those in the GI tract and blood vessels [254], and for antisense ODNs delivery [259]. Other applications include advances in ex vivo tissue engineering, development of tumor vaccines, localized therapy for cancer, and cardiovascular therapy [260]. Significant enhancement in reporter gene expression in a short time has been observed in the ex vivo porcine airway model; this may be attributed to an increase in contact time with mucociliary cells, thereby reducing their clearance from the target site [261]. A study carried out using magnetic albumin microspheres with entrapped doxorubicin in the rat model for tumors resulted in a high level of tumor remission in animals compared to animals treated with free doxorubicin, placebo microspheres, or nonlocalized doxorubicin microspheres, which resulted in considerable enlargement in tumor size associated with metastases and subsequent death [262,263]. The magnetic nanoparticles with doxorubicin are also under clinical trial [264]. Magnetofection has been widely used for viral and nonviral vectors and also for the delivery of DNA, nucleic acids, and siRNA [260,265,266].
In conclusion, magnetofection is an efficient system for gene delivery and has the potential to bring in vitro and in vivo transgene transfection in the target organ. The limitations of this delivery system are overcome by the application of proper formulations and novel magnetic field skills.View chapter
Nonviral vectors group a heterogeneous variety of elements that can be classified as naked DNA or RNA, liposome-DNA complexes (lipoplexes), and polymer-DNA complexes (polyplexes). Since the beginning of the gene therapy field, nonviral vectors have received significant attention due to their reduced pathogenicity, lower immunotoxicity, and low cost and ease of production over viral approaches. To date, a myriad of delivery systems grouped as physical methods and chemical carriers have been reported. Physical methods such as direct injection, ballistic DNA, electroporation, sonoporation, photoporation, magnetofection, hydroporation, and mechanical massage, employ physical force to cross the cell membrane barrier. Chemical carriers such as (1) inorganic particles (calcium phosphate, silica, gold, but also magnetic nanoparticles, fullerenes, carbon nanotubes, quantum dots, and supramolecular systems); (2) lipid-based (cationic lipids, lipid-nano emulsions, solid lipid nanoparticles); (3) peptide-based; and (4) polymer-based (i.e., polyethylenimine, chitosan, dendrimers, and polymethacrylate) form small size complexes with nucleic acids to help them cross the cell membrane efficiently (see ref [29] for extensive review). However, despite the large number of different nonviral vectors still, there is poor transduction efficiency of the target cells as well as low and transient transgene expression. Due to it, nonviral vectors account for less than 25% of the clinical assays, mainly for cancer and cardiovascular diseases, being naked/plasmid DNA (452 clinical assays) and lipofection (119 clinical assays) the systems more frequently used, while all the rest of the nonviral vector account only for 3% of the assays.View chapter
To be continued? Our work and existence, as media and people, is funded solely by our most generous supporters. But we’re not really covering our costs so far, and we’re in dire needs to upgrade our equipment, especially for video production. Help SILVIEW.media survive and grow, please donate here, anything helps. Thank you!
! Articles can always be subject of later editing as a way of perfecting them
Initially I didn’t pay much attention to these reports because first ones were pretty vague and seemed unsubstantiated. They kind of were. But then they started to become more and more detailed, coherent and very specific. My own research on #biohacking started to intersect more often, to the point where today they almost coincide.
Video by Tim Truth
To better understand where I’m coming from, your journey needs to start here:
SOUTH SAN FRANCISCO, Calif., July 12, 2016 /PRNewswire/ — Profusa, Inc., a leading developer of tissue-integrated biosensors, today announced that it was awarded a $7.5 million dollar grant from the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army Research Office (ARO) to develop implantable biosensors for the simultaneous, continuous monitoring of multiple body chemistries. Aimed at providing real-time monitoring of a combat soldier’s health status to improve mission efficiency, the award supports further development of the company’s biosensor technology for real-time detection of the body’s chemical constituents. DARPA and ARO are agencies of the U.S. Department of Defense focused on the developing emerging technologies for use by the military.
“Profusa’s vision is to replace a point-in-time chemistry panel that measures multiple biomarkers, such as oxygen, glucose, lactate, urea, and ions with a biosensor that provides a continuous stream of wireless data,” said Ben Hwang, Ph.D., Profusa’s chairman and chief executive officer. “DARPA’s mission is to make pivotal investments in breakthrough technologies for national security. We are gratified to be awarded this grant to accelerate the development of our novel tissue-integrating sensors for application to soldier health and peak performance.”
Tissue-integrating Biosensors for Multiple Biomarkers Supported by DARPA, ARO and the National Institutes of Health, Profusa’s technology and unique bioengineering approach overcomes the largest hurdle in long-term use of biosensors in the body: the foreign body response. Placed just under the skin with a specially designed injector, each tiny biosensor is a flexible fiber, 2 mm-to-5 mm long and 200-500 microns in diameter. Rather than being isolated from the body, Profusa’s biosensors work fully integrated within the body’s tissue — without any metal device or electronics — overcoming the effects of the foreign body response for more than one year.
Each biosensor is comprised of a bioengineered “smart hydrogel” (similar to contact lens material) forming a porous, tissue-integrating scaffold that induces capillary and cellular in-growth from surrounding tissue. A unique property of the smart gel is its ability to luminesce upon exposure to light in proportion to the concentration of a chemical such as oxygen, glucose or other biomarker.
“Long-lasting, implantable biosensors that provide continuous measurement of multiple body chemistries will enable monitoring of a soldier’s metabolic and dehydration status, ion panels, blood gases, and other key physiological biomarkers,” said Natalie Wisniewski, Ph.D., the principal investigator leading the grant work and Profusa’s co-founder and chief technology officer. “Our ongoing program with DARPA builds on Profusa’s tissue-integrating sensor that overcomes the foreign body response and serves as a technology platform for the detection of multiple analytes.”
Lumee Oxygen Sensing System™ Profusa’s first medical product, the Lumee Oxygen Sensing System, is a single-biomarker sensor designed to measure oxygen. In contrast to blood oxygen reported by other devices, the system incorporates the only technology that can monitor local tissue oxygen. When applied to the treatment of peripheral artery disease (PAD), it prompts the clinician to provide therapeutic action to ensure tissue oxygen levels persist throughout the treatment and healing process.
Pending CE Mark, the Lumee system is slated to be available in Europe in 2016 for use by vascular surgeons, wound-healing specialists and other licensed healthcare providers who may benefit in monitoring local tissue oxygen. PAD affects 202 million people worldwide, 27 million of whom live in Europe and North America, with an annual economic burden of more than $74 billion in the U.S. alone.
Profusa, Inc. Profusa, Inc., based in South San Francisco, Calif., is leading the development of novel tissue-integrated sensors that empowers an individual with the ability to monitor their unique body chemistry in unprecedented ways to transform the management of personal health and disease. Overcoming the body’s response to foreign material for long-term use, its technology promises to be the foundational platform of real-time biochemical detection through the development of tiny bioengineered sensors that become one with the body to detect and continuously transmit actionable, medical-grade data for personal and medical use. See http://www.profusa.com for more information.
The research is based upon work supported by DARPA, the Biological Technologies Office (BTO), and ARO grant [W911NF-16-1-0341]. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of DARPA, BTO, the ARO, or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright annotation thereon.
So I can’t say with 100% certainty that what DARPA did and what people found are one and the same thing, but this hits close enough, if this is possible, that is possible, and altogether give 200% x reasons to freak out.
I will keep adding resources and details here, but my point is made.
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Sometimes my memes are 3D. And you can own them. Or send them to someone. You can even eat some of them. CLICK HERE
I don’t know if they do it, because no independent researchers examine those swabs, but I have always pointed out that our overlords seem more concerned with testing than with vaccinating. Almost like the vaccines were the bait and tests were the switch. And now we also know they totally CAN do that. Just follow the science below.
The respectable Mr. David Knight makes a summary of our article
UPDATE: LMAO, THIS WENT SO VIRAL VICE WAS SENT TO DEBUNK IT, SEE FOR YOURSELF, IT’S HILARIOUS!
Our comment has already been deleted, apparently, or I can’t find it anymore 😀
Attn: Gates-paid fact-checkers – Injectable computers with RFID antennas produced in 2016
UPDATE: DR. LORRAINE DAY QUOTES AND FURTHER EXPLAINS THIS VERY ARTICLE!
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November 3, 2020
Researchers engineer tiny machines that deliver medicine efficiently
A theragripper is about the size of a speck of dust. This swab contains dozens of the tiny devices. Credit: Johns Hopkins University.
Inspired by a parasitic worm that digs its sharp teeth into its host’s intestines, Johns Hopkins researchers have designed tiny, star-shaped microdevices that can latch onto intestinal mucosa and release drugs into the body.
David Gracias, Ph.D., a professor in the Johns Hopkins University Whiting School of Engineering, and Johns Hopkins gastroenterologist Florin M. Selaru, M.D., director of the Johns Hopkins Inflammatory Bowel Disease Center, led a team of researchers and biomedical engineers that designed and tested shape-changing microdevices that mimic the way the parasitic hookworm affixes itself to an organism’s intestines.
Made of metal and thin, shape-changing film and coated in a heat-sensitive paraffin wax, “theragrippers,” each roughly the size of a dust speck, potentially can carry any drug and release it gradually into the body.
The team published results of an animal study this week as the cover article in the journal Science Advances.
Gradual or extended release of a drug is a long-sought goal in medicine. Selaru explains that a problem with extended-release drugs is they often make their way entirely through the gastrointestinal tract before they’ve finished dispensing their medication.
“Normal constriction and relaxation of GI tract muscles make it impossible for extended-release drugs to stay in the intestine long enough for the patient to receive the full dose,” says Selaru, who has collaborated with Gracias for more than 10 years. “We’ve been working to solve this problem by designing these small drug carriers that can autonomously latch onto the intestinal mucosa and keep the drug load inside the GI tract for a desired duration of time.”
When an open theragripper, left, is exposed to internal body temperatures, it closes on the instestinal wall. In the gripper’s center is a space for a small dose of a drug. Credit: Johns Hopkins University
Thousands of theragrippers can be deployed in the GI tract. When the paraffin wax coating on the grippers reaches the temperature inside the body, the devices close autonomously and clamp onto the colonic wall. The closing action causes the tiny, six-pointed devices to dig into the mucosa and remain attached to the colon, where they are retained and release their medicine payloads gradually into the body. Eventually, the theragrippers lose their hold on the tissue and are cleared from the intestine via normal gastrointestinal muscular function.
Taken from the original research annexes
Gracias notes advances in the field of biomedical engineering in recent years.
“We have seen the introduction of dynamic, microfabricated smart devices that can be controlled by electrical or chemical signals,” he says. “But these grippers are so small that batteries, antennas and other components will not fit on them.”
Theragrippers, says Gracias, don’t rely on electricity, wireless signals or external controls. “Instead, they operate like small, compressed springs with a temperature-triggered coating on the devices that releases the stored energy autonomously at body temperature.”
The Johns Hopkins researchers fabricated the devices with about 6,000 theragrippers per 3-inch silicon wafer. In their animal experiments, they loaded a pain-relieving drug onto the grippers. The researchers’ studies found that the animals into which theragrippers were administered had higher concentrates of the pain reliever in their bloodstreams than did the control group. The drug stayed in the test subjects’ systems for nearly 12 hours versus two hours in the control group.
“You could put the computational power of the spaceship Voyager onto an object the size of a cell”. In 2018.
“Swarms of microscopic robots that can be injected” Tell Melinda Gates we can inject robots and computers these days.
HERE’S A VERY SIMPLE WAY TO ATTACK THE BRAIN THROUGH THE TEST SWABS
I’ve seen a report on someone who had to undergo tests almost daily and he developed brain cancer over the course of about three months. But I can’t verify it, so that’s all it’s worth.
“Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.”
Report contents include:
Market analysis of nano-based diagnostic tests for COVID-19 including nanosensors incorporating gold nanoparticles, iron oxide nanoparticles, graphene, quantum dots, carbon quantum dots and carbon nanotubes. Market revenues adjusted to pandemic outcomes. In-depth company profiles. Companies profiled include Abbott Laboratories, Cardea, Ferrotec (USA) Corporation, E25Bio, Grolltex, Inc., Luminex Corporation etc.
Currently, many studies are being conducted on developing a method for delivering nanoparticles into the nasal cavity as a safe and more effective countermeasure against viral infection and treatment.180 Since SARS-CoV-2 initiates infection on the mucosal surface of the eye or nasal cavity, mucosal therapy is the most important strategy for treating such infectious diseases. Delivery through the nasal cavity is not only simple and inexpensive but also non-invasive, and the NP is rapidly absorbed due to the cavity’s abundant capillary plexus and large surface area.181 The properties of the NPs, such as the surface charge, size, and shape, are important factors to be considered while optimizing the method of delivery to the nasal cavity and play a critical role in effective and safe treatment.182 Studies have been conducted using small animals to evaluate the system that is delivered to the lungs by administering NPs to the nasal cavity. Therefore, findings of these animal studies cannot be easily generalized to humans. To date, three types of NPs (organic, inorganic, and virus-like NPs) have been designed with delivery capabilities that are suitable for therapeutic purposes, which can also be administered intranasally for effective delivery.
Nasal-nanotechnology: revolution for efficient therapeutics delivery
Context: In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose.
Objective: The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration.
Methods: Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration.
Results and conclusion: The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.
International Journal of Pharmaceutics 2008 May 22;
Abstract
The field of nanotechnology may hold the promise of significant improvements in the health and well being of patients, as well as in manufacturing technologies. The knowledge of this impact of nanomaterials on public health is limited so far. This paper briefly reviews the unique size-controlled properties of nanomaterials, their disposition in the body after inhalation, and the factors influencing the fate of inhaled nanomaterials. The physiology of the lung makes it an ideal target organ for non-invasive local and systemic drug delivery, especially for protein and poorly water-soluble drugs that have low oral bioavailability via oral administration. The potential application of pulmonary drug delivery of nanoparticles to the lungs, specifically in context of published results reported on nanomaterials in environmental epidemiology and toxicology is reviewed in this paper.
Advanced Drug Delivery Review. 2009 Feb 27; doi: 10.1016/j.addr.2008.09.005. Epub 2008 Dec 13.
Abstract
The great interest in mucosal vaccine delivery arises from the fact that mucosal surfaces represent the major site of entry for many pathogens. Among other mucosal sites, nasal delivery is especially attractive for immunization, as the nasal epithelium is characterized by relatively high permeability, low enzymatic activity and by the presence of an important number of immunocompetent cells. In addition to these advantageous characteristics, the nasal route could offer simplified and more cost-effective protocols for vaccination with improved patient compliance. The use of nanocarriers provides a suitable way for the nasal delivery of antigenic molecules. Besides improved protection and facilitated transport of the antigen, nanoparticulate delivery systems could also provide more effective antigen recognition by immune cells. These represent key factors in the optimal processing and presentation of the antigen, and therefore in the subsequent development of a suitable immune response. In this sense, the design of optimized vaccine nanocarriers offers a promising way for nasal mucosal vaccination.
The great interest in mucosal vaccine delivery arises from the fact that mucosal surfaces represent the major site of entry for many pathogens. Among other mucosal sites, nasal delivery is especially attractive for immunization, as the nasal epithelium is characterized by relatively high permeability, low enzymatic activity and by the presence of an important number of immunocompetent cells. In addition to these advantageous characteristics, the nasal route could offer simplified and more cost-effective protocols for vaccination with improved patient compliance. The use of nanocarriers provides a suitable way for the nasal delivery of antigenic molecules. Besides improved protection and facilitated transport of the antigen, nanoparticulate delivery systems could also provide more effective antigen recognition by immune cells. These represent key factors in the optimal processing and presentation of the antigen, and therefore in the subsequent development of a suitable immune response. In this sense, the design of optimized vaccine nanocarriers offers a promising way for nasal mucosal vaccination.
Context: Brain disorders remain the world’s leading cause of disability, and account for more hospitalizations and prolonged care than almost all other diseases combined. The majority of drugs, proteins and peptides do not readily permeate into brain due to the presence of the blood-brain barrier (BBB), thus impeding treatment of these conditions.
Objective: Attention has turned to developing novel and effective delivery systems to provide good bioavailability in the brain.
Methods: Intranasal administration is a non-invasive method of drug delivery that may bypass the BBB, allowing therapeutic substances direct access to the brain. However, intranasal administration produces quite low drug concentrations in the brain due limited nasal mucosal permeability and the harsh nasal cavity environment. Pre-clinical studies using encapsulation of drugs in nanoparticulate systems improved the nose to brain targeting and bioavailability in brain. However, the toxic effects of nanoparticles on brain function are unknown.
Result and conclusion: This review highlights the understanding of several brain diseases and the important pathophysiological mechanisms involved. The review discusses the role of nanotherapeutics in treating brain disorders via nose to brain delivery, the mechanisms of drug absorption across nasal mucosa to the brain, strategies to overcome the blood brain barrier, nanoformulation strategies for enhanced brain targeting via nasal route and neurotoxicity issues of nanoparticles.
The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.
Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.
Nanoparticles for nasal vaccination. Csaba N, Garcia-Fuentes M, Alonso MJ.Csaba N, et al.Adv Drug Deliv Rev. 2009 Feb 27;61(2):140-57. doi: 10.1016/j.addr.2008.09.005. Epub 2008 Dec 13.Adv Drug Deliv Rev. 2009.PMID: 19121350 Review.
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