Is Nanotechnology helping in the fight against Covid 19, or Cancer?

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Robotic cells to fight cancer tumors

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How Doctors and Robots Are Battling Hard-to-Reach Cancers | UPMC

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This Robot Can Diagnose Lung Cancer

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Nanorobots in the Body: The Future of Medicine

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Video Journey Into Nanotechnology

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Nanotechnology and COVID-19 research – a virtual Q&A hosted by Nature Nanotechnology

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Researchers develop novel nanoadjuvant COVID-19 vaccine candidate

3/29/21


https://www.news-medical.net/news/20210 ... idate.aspx


Finding effective and safe vaccines is crucial in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the coronavirus disease 2019 (COVID-19).

As a vital component of a subunit vaccine, the adjuvant strengthens the antigen-induced immune responses.

Researchers at the National Center for Nanoscience and Technology of China, the Chinese Academy of Sciences (CAS), introduced a new vaccine, which compromises the spike protein’s receptor-binding domain (RBD) and the manganese nanoadjuvant (MnARK), inducing humoral and cellular responses.

The study, recently published in the journal Nanotoday, highlights the potential of a MnARK-based nanovaccine to prevent SARS-CoV-2 infection. The vaccine is a programmable platform that can enhance the co-delivery efficiency of RBD antigen and a nanoadjuvant to lymph nodes.

Study background

More than 125.85 million cases of COVID-19 have been reported worldwide since the virus was first detected in Wuhan, China, in December 2019. Of these, 2.76 million people have lost their lives. One effective way to prevent infection is through vaccination.

Multiple novel coronavirus vaccines have shown promising results, with many being used in vaccine campaigns in many parts of the world.

Yet, the limited production capacity would negatively impact herd immunity and slow down pandemic control measures. One way to boost vaccine production and use is by using a suitable adjuvant to the subunit vaccine, which can improve weak RBD immunogenicity, reduce the number of vaccinations and antigen dosage, and trigger potent neutralizing antibodies to combat the pandemic.

Currently, Alum adjuvant is the only approved and safe one used. It helps the antigen to produce a more robust immune response than a free antigen. The lack of cellular immune response limits Alum-formulated vaccines.

However, the manganese (Mn) nanoparticle adjuvant may be another suitable candidate. Exhibiting the potential to stimulate innate immune responses, it has been used in developing cancer vaccines.

To date, the design and structure of vaccine systems that provide satisfactory antigen delivery and immune cell activation are significant concerns for protein subunit-based vaccines. The unique size of functional nanomaterials aid in the delivery of vaccine components to vital immune cells or lymphoid tissues, improving the immune response to combat infection.

Meanwhile, LNs are restrictive in size, making it hard to deliver the vaccine to immune cells. Hence, designing a simple approach to delivery the antigen and adjuvant and activating the adaptive and innate immune responses are essential for novel coronavirus subunit vaccines.

The study

The researchers constructed a nanovaccine through albumin to concurrently deliver antigen and adjuvant to lymph nodes. The team noted that an antigen-adjuvant-formulated nanovaccine, at about 10 to 100 nm, would accumulate in LNs after injection.

The constructed nanovaccine contains the RBD antigen of the S1 protein and the manganese nanoadjuvant (MnARK), a negatively charged cubic manganese oxide nanoparticle known to active the cGAS-STING pathway and transport RBD antigens to the lymph nodes.

Compared with the traditional Alum-adsorbed RBD vaccine, the nanovaccine markedly increased RBD-specific immunoglobulin G (IgG) and immunoglobulin M (IgM) responses by 10-fold and 5-fold, respectively. It also enhanced the neutralization of the SARS-CoV-2 based on both pseudovirus and live virus, by 270-fold and 8-fold, respectively.

Further, the nanovaccine induced wider and more robust T-cell responses than the conventional Alu-RBD vaccine, stimulating the cGAS-STING pathway and inducing a high-quality immune reaction.

Importantly, a potent neutralizing antibody response induced by MnARK nanovaccine strongly supports its promising potential for realizing a satisfactory protective immunity against novel coronavirus,” the researchers wrote in the paper.

The low cost of the nanovaccine makes it possible for clinical investigation in future studies. The team hopes the nanovaccine can be used to combat the spreading pandemic, as it has many advantages over other types of vaccines.


The combination of an adjuvant with the RBD protein in a MnARK nanovaccine may be an ideal strategy for the development of vaccines to combat novel coronavirus or other coronaviruses,” the researchers added.

Source:


COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) - https://gisanddata.maps.arcgis.com/apps ... 7b48e9ecf6

Journal reference:

Wang, Y., Xie, Y., Luo, J., Guo, M. et al. (2021). Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus. Nanotoday. https://doi.org/10.1016/j.nantod.2021.101139, https://www.sciencedirect.com/science/a ... 5sPuY4xrtw
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Scientists use nanotechnology to detect bone-healing stem cells

3/29/21


https://phys.org/news/2021-03-scientist ... cells.html


Researchers at the University of Southampton have developed a new way of using nanomaterials to identify and enrich skeletal stem cells—a discovery which could eventually lead to new treatments for major bone fractures and the repair of lost or damaged bone.

Working together, a team of physicists, chemists and tissue engineering experts used specially designed gold nanoparticles to 'seek out' specific human bone stem cells—creating a fluorescent glow to reveal their presence among other types of cells and allow them to be isolated or 'enriched'.

The researchers concluded their new technique is simpler and quicker than other methods and up to 50-500 times more effective at enriching stem cells.

The study, led by Professor of Musculoskeletal Science, Richard Oreffo and Professor Antonios Kanaras of the Quantum, Light and Matter Group in the School of Physics and Astronomy, is published in ACS Nano—an internationally recognized multidisciplinary journal.

In laboratory tests, the researchers used gold nanoparticles—tiny spherical particles made up of thousands of gold atoms—coated with oligonucleotides (strands of DNA), to optically detect the specific messenger RNA (mRNA) signatures of skeletal stem cells in bone marrow. When detection takes place, the nanoparticles release a fluorescent dye, making the stem cells distinguishable from other surrounding cells, under microscopic observation. The stem cells can then be separated using a sophisticated fluorescence cell sorting process.

Stem cells are cells that are not yet specialized and can develop to perform different functions. Identifying skeletal stems cells allows scientists to grow these cells in defined conditions to enable the growth and formation of bone and cartilage tissue—for example, to help mend broken bones.

Among the challenges posed by our aging population is the need for novel and cost-effective approaches to bone repair. With one in three women and one in five men at risk of osteoporotic fractures worldwide, the costs are significant, with bone fractures alone costing the European economy €17 billion and the US economy $20 billion annually.

Within the University of Southampton's Bone and Joint Research Group, Professor Richard Oreffo and his team have been looking at bone stem cell based therapies for over 15 years to understand bone tissue development and to generate bone and cartilage. Over the same time-period, Professor Antonios Kanaras and his colleagues in the Quantum, Light and Matter Group have been designing novel nanomaterials and studying their applications in the fields of biomedical sciences and energy. This latest study effectively brings these disciplines together and is an exemplar of the impact collaborative, interdisciplinary working can bring.

Professor Oreffo said: "Skeletal stem cell based therapies offer some of the most exciting and promising areas for bone disease treatment and bone regenerative medicine for an aging population. The current studies have harnessed unique DNA sequences from targets we believe would enrich the skeletal stem cell and, using Fluorescence Activated Cell Sorting (FACS) we have been able to enrich bone stem cells from patients. Identification of unique markers is the holy grail in bone stem cell biology and, while we still have some way to go; these studies offer a step change in our ability to target and identify human bone stem cells and the exciting therapeutic potential therein."

Professor Oreffo added: "Importantly, these studies show the advantages of interdisciplinary research to address a challenging problem with state of the art molecular/cell biology combined with nanomaterials' chemistry platform technologies."

Professor Kanaras said: "The appropriate design of materials is essential for their application in complex systems. Customizing the chemistry of nanoparticles we are able to program specific functions in their design.

"In this research project, we designed nanoparticles coated with short sequences of DNA, which are able to sense HSPA8 mRNA and Runx2 mRNA in skeletal stem cells and together with advanced FACS gating strategies, to enable the assortment of the relevant cells from human bone marrow.

"An important aspect of the nanomaterial design involves strategies to regulate the density of oligonucleotides on the surface of the nanoparticles, which help to avoid DNA enzymatic degradation in cells. Fluorescent reporters on the oligonucleotides enable us to observe the status of the nanoparticles at different stages of the experiment, ensuring the quality of the endocellular sensor."

Both lead researchers also recognize that the accomplishments were possible due to the work of all the experienced research fellows and Ph.D. students involved in this research as well as collaboration with Professor Tom Brown and Dr. Afaf E-Sagheer of the University of Oxford, who synthesized a large variety of functional oligonucleotides.

The scientists are currently applying single cell RNA sequencing to the platform technology developed with partners in Oxford and the Institute for Life Sciences (IfLS) at Southampton to further refine and enrich bone stem cells and assess functionality. The team propose to then move to clinical application with preclinical bone formation studies to generate proof of concept studies.

More information:
Miguel Xavier et al, Enrichment of Skeletal Stem Cells from Human Bone Marrow Using Spherical Nucleic Acids, ACS Nano (2021). DOI: 10.1021/acsnano.0c10683
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Method offers inexpensive imaging at the scale of virus particles

3/29/21

https://phys.org/news/2021-03-method-in ... virus.html

Using an ordinary light microscope, MIT engineers have devised a technique for imaging biological samples with accuracy at the scale of 10 nanometers—which should enable them to image viruses and potentially even single biomolecules, the researchers say.

The new technique builds on expansion microscopy, an approach that involves embedding biological samples in a hydrogel and then expanding them before imaging them with a microscope. For the latest version of the technique, the researchers developed a new type of hydrogel that maintains a more uniform configuration, allowing for greater accuracy in imaging tiny structures.

This degree of accuracy could open the door to studying the basic molecular interactions that make life possible, says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology, a professor of biological engineering and brain and cognitive sciences at MIT, and a member of MIT's McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research.

"If you could see individual molecules and identify what kind they are, with single-digit-nanometer accuracy, then you might be able to actually look at the structure of life. And structure, as a century of modern biology has told us, governs function," says Boyden, who is the senior author of the new study.

The lead authors of the paper, which appears today in Nature Nanotechnology, are MIT Research Scientist Ruixuan Gao and Chih-Chieh "Jay" Yu Ph.D. '20. Other authors include Linyi Gao Ph.D. '20; former MIT postdoc Kiryl Piatkevich; Rachael Neve, director of the Gene Technology Core at Massachusetts General Hospital; James Munro, an associate professor of microbiology and physiological systems at University of Massachusetts Medical School; and Srigokul Upadhyayula, a former assistant professor of pediatrics at Harvard Medical School and an assistant professor in residence of cell and developmental biology at the University of California at Berkeley.

Low cost, high resolution

Many labs around the world have begun using expansion microscopy since Boyden's lab first introduced it in 2015. With this technique, researchers physically enlarge their samples about fourfold in linear dimension before imaging them, allowing them to generate high-resolution images without expensive equipment. Boyden's lab has also developed methods for labeling proteins, RNA, and other molecules in a sample so that they can be imaged after expansion.

"Hundreds of groups are doing expansion microscopy. There's clearly pent-up demand for an easy, inexpensive method of nanoimaging," Boyden says. "Now the question is, how good can we get? Can we get down to single-molecule accuracy? Because in the end, you want to reach a resolution that gets down to the fundamental building blocks of life."

Other techniques such as electron microscopy and super-resolution imaging offer high resolution, but the equipment required is expensive and not widely accessible. Expansion microscopy, however, enables high-resolution imaging with an ordinary light microscope.

In a 2017 paper, Boyden's lab demonstrated resolution of around 20 nanometers, using a process in which samples were expanded twice before imaging. This approach, as well as the earlier versions of expansion microscopy, relies on an absorbent polymer made from sodium polyacrylate, assembled using a method called free radical synthesis. These gels swell when exposed to water; however, one limitation of these gels is that they are not completely uniform in structure or density. This irregularity leads to small distortions in the shape of the sample when it's expanded, limiting the accuracy that can be achieved.

To overcome this, the researchers developed a new gel called tetra-gel, which forms a more predictable structure. By combining tetrahedral PEG molecules with tetrahedral sodium polyacrylates, the researchers were able to create a lattice-like structure that is much more uniform than the free-radical synthesized sodium polyacrylate hydrogels they previously used.

The researchers demonstrated the accuracy of this approach by using it to expand particles of herpes simplex virus type 1 (HSV-1), which have a distinctive spherical shape. After expanding the virus particles, the researchers compared the shapes to the shapes obtained by electron microscopy and found that the distortion was lower than that seen with previous versions of expansion microscopy, allowing them to achieve an accuracy of about 10 nanometers.

"We can look at how the arrangements of these proteins change as they are expanded and evaluate how close they are to the spherical shape. That's how we validated it and determined how faithfully we can preserve the nanostructure of the shapes and the relative spatial arrangements of these molecules," Ruixuan Gao says.

Single molecules

The researchers also used their new hydrogel to expand cells, including human kidney cells and mouse brain cells. They are now working on ways to improve the accuracy to the point where they can image individual molecules within such cells. One limitation on this degree of accuracy is the size of the antibodies used to label molecules in the cell, which are about 10 to 20 nanometers long. To image individual molecules, the researchers would likely need to create smaller labels or to add the labels after expansion was complete.

They are also exploring whether other types of polymers, or modified versions of the tetra-gel polymer, could help them realize greater accuracy.

If they can achieve accuracy down to single molecules, many new frontiers could be explored, Boyden says. For example, scientists could glimpse how different molecules interact with each other, which could shed light on cell signaling pathways, immune response activation, synaptic communication, drug-target interactions, and many other biological phenomena.

"We'd love to look at regions of a cell, like the synapse between two neurons, or other molecules involved in cell-cell signaling, and to figure out how all the parts talk to each other," he says. "How do they work together and how do they go wrong in diseases?"

More information:
A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy, Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-00875-7 , dx.doi.org/10.1038/s41565-021-00875-7
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Self-healing “Xenobots” mean a future with living machines

4/1/21

https://www.inverse.com/innovation/xeno ... g-machines


One hundred years ago, it was easy to tell when something was a machine. Machines were “hard and clanky, metallic, and pretty heavy,” as developmental biologist Michael Levin tells Inverse.

But lately, it’s become clear to Levin and his collaborator Joshua Bongard, a professor of computer science at the University of Vermont, that our definitions of “machine” and “living organism” are about to get really, really murky.

In January of 2020, the two first made headlines after announcing their team had successfully created “completely biological machines.” Now, Levin and Bongard have taken their biological machines, or “Xenobots,” to the next level — using frog cells to create life forms capable of motion, memory, and manipulation of the world around them.

These incredible results were published Wednesday in the journal Science Robotics.

The background — The 2020 biological machines were designed in computer simulations, then built in Petri dishes using micro-scalpels and living biological tissues — skin and muscle cells harvested from embryos of the African clawed frog, Xenopus laevis. In other words, they’re designed like one would design a robot, but the raw materials are 100 percent living cells.

Levin and Bongard landed on a design reminiscent of the dog-turned-ottoman from Beauty and the Beast that, once carved into shape, would actually contract its muscle cells and walk across the dish. They called their living creations Xenobots (pronounced zenno-bot), after the frog that donated its cells.

“Already in that first paper we showed some creatures whose evolutionary history took place in a computer,” Levin, a professor at Tufts University, says.

“They had an evolutionary history, it just wasn’t on Earth. It was in this completely virtual world that Josh Bongard coded up.”

A few weeks ago, Bongard published his new theory on whether it’s helpful to still use the metaphor that living things are like machines (spoiler: It’s not). In the team’s latest bot advance, there’s no sculpting needed. The new Xenobots aren’t ottomans, they’re spheres. And they don’t have muscle cells, they’re all skin. But they still move around just fine.

What’s new — The skin of a Xenopus frog is covered in cilia, tiny hairlike structures, which redistribute mucus across their skin. It’s an adaptation to keep bacteria and fungi at bay. When you put embryonic skin cells together, they conglomerate into little spheres with the cilia on the outside.

The team found that the cilia on this new Xenobot “work in concert so the thing can go forward,” Levin says. “They start to row and the thing moves.”

The researchers also tested to see if they could set the Xenobots up with a form of rudimentary memory. They injected them with RNA that encodes a protein that changes color when it’s exposed to a certain color of light. It worked: The bots made the proteins, and it was clear which bots had “seen” the light when they came back a different color.

“It’s a proof of principle that we can modify the cells to put in other things that give them new functionalities,” says Levin. “Synthetic biology nowadays is all ‘cell soups,’ it’s all cells in culture. Now they can be embodied — we have a body into which you can put all of these kinds of circuits.”

The team was also interested in how the Xenobots would act as a group. Bongard ran more computational simulations to try and predict what would happen when you let the bots into an arena with a bunch of particles. How would the bots’ motion redistribute the particles? Can you get them to make them into piles?

It was an iterative process, measuring properties of the Xenobots, putting the data into the computer simulation to make predictions, then testing those predictions on the bots and measuring again. “It goes simulation, experiment, simulation, experiment, and hopefully each time we’re a bit smarter after each go-round,” Levin says.

Why this matters — Practically speaking, Xenobots could have applications like swimming through the bloodstream and unclogging arteries. But Levin is more excited about the big picture.

“Most of the problems of modern medicine would go away... if we understood how to make cells build whatever we want them to build.”

When Xenobots grow over their short 10-day lifespan, they elongate and become transparent.

“They almost look like ghosts,” Levin says. “And it’s nothing you would have predicted, they don’t look like frog embryos, they don’t look like tadpoles. They have their own brand-new developmental sequence.”

It’s a whole new type of model organism, Levin explains, that will help us understand how cells build structures, and how we can “motivate them” to make different things besides their genetic default — no genetic engineering required.

“Most of the problems of modern medicine would go away… if we understood how to make cells build whatever we want them to build,” he says.

When probed about whether it was just an accident that this configuration of ciliated cells can move, Levin pushed back at the question. He says a lot of people don’t take evolution seriously enough.

“Our own complex cognitive properties evolved from humbler, simpler versions of those exact same properties in other [earlier] organisms,” he says.

“[Are the Xenobots] using physics to repurpose their mechanisms in a way that’s explainable by chemistry and physics? Of course they are. There’s no magic. But it’s the same for us. When we walk around, we’re using the electricity of electrical networks in our brains to activate our muscles. That doesn’t mean it’s any less wondrous.”

“People are very binary in things. They say is it a robot, or is it an organism? Yes and yes,” says Levin. “These binary classifications are just no good anymore.”

What’s next? — Levin and his team are moving forward with their experiments, including some using cells from sources beyond frogs. He’s driven by his curiosity about how groups of cells work together to form a sort of collective intelligence — just like our human brains.

“That’s a problem that’s kept me awake since I was a kid,” he says. “How does the structure of the body relate to the mind that lives in there somehow?”

As these living bots get more and more complex, society will have to grapple with what it means to be cognitive. Levin imagines a future straight out of a science fiction movie — one that will challenge how we view cognition, and what we ethically owe our creations.

“In your lifetime, we’re going to be surrounded by just an incredible plethora of new agents that are weird hybrids and cyborgs and robots with living tissue embedded and [vice versa] — every combination under the sun is going to be running around somewhere,” says Levin.

Abstract: Robot swarms have, to date, been constructed from artificial materials. Motile biological constructs have been created from muscle cells grown on precisely shaped scaffolds. However, the exploitation of emergent self-organization and functional plasticity into a self-directed living machine has remained a major challenge. We report here a method for generation of in vitro biological robots from frog (Xenopus laevis) cells. These xenobots exhibit coordinated locomotion via cilia present on their surface. These cilia arise through normal tissue patterning and do not require complicated construction methods or genomic editing, making production amenable to high-throughput projects. The biological robots arise by cellular self-organization and do not require scaffolds or microprinting; the amphibian cells are highly amenable to surgical, genetic, chemical, and optical stimulation during the self-assembly process. We show that the xenobots can navigate aqueous environments in diverse ways, heal after damage, and show emergent group behaviors. We constructed a computational model to predict useful collective behaviors that can be elicited from a xenobot swarm. In addition, we provide proof of principle for a writable molecular memory using a photoconvertible protein that can record exposure to a specific wavelength of light. Together, these results introduce a platform that can be used to study many aspects of self-assembly, swarm behavior, and synthetic bioengineering, as well as provide versatile, soft-body living machines for numerous practical applications in biomedicine and the environment.
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