Shaping Stem Cell Research with Nanotechnology – Hope for Treating Parkinson’s; Heart Disease and ???


Nanoscientists have developed a technique that allows them to transform stem cells into bone cells on command. But could the process be used to treat deadly conditions such as heart disease and Parkinson’s?

Anyone who knows a thing or two about biology knows that stem cells have tremendous potential in medicine: anything from repairing and replenishing heart cells after an attack to replacing nerve cells that are progressively lost in the brain of a person with Parkinson’s.

One of the big challenges of using stem cells as a therapy is coaxing them to grow into the specific type of tissue that is required. In the body this happens thanks to precise chemical and physical signals, not all of which are yet understood or characterised.

Using chemicals to direct the fate of stem cells has worked in laboratories, but the outcomes are not always safe or predictable.

Now, a team from Northwestern University in the US thinks it has a solution. They say that they can direct the developmental fate of stem cells using only physical cues, by adapting a well-known technique that traces three-dimensional microscopic shapes and reconstructs them on flat surfaces.

The process is called scanning probe lithography.

By placing the stem cells on the nanopatterned surface, and without adding any kind of chemicals, the scientists found that they could induce the stem cells to develop into bone cells.

Extend this technique, they say, and it might be possible to turn stem cells into any type of cell on command.

When the body needs a repair to be carried out, a special type of stem cell – called mesenchymal stem cells or MSCs – can enter the blood circulation system. These cells travel around the body and actually home in on where they are needed.

MSCs have the potential to develop into a whole range of different tissue types – in other words, they are pluripotent.

The developmental decision that they make depends, in part, on the molecular structures in the matrix surrounding the cells that make up the tissue.

The structure of the matrix affects the softness of the tissue – so the brain is a soft, mushy tissue, while stiffer tissues include muscle, and rigid tissues include bone.

The US team has mimicked this real-life situation. Using the molecular structures in the matrix that surround a cell as a pattern, and with an array of pyramid-like points that are a hundred-thousand times smaller than the tip of a pencil and incredibly sharp, molecule by molecule they have built up a kind of nano-landscape with sculptures ranging in size from the nano- to the microscale, on a small piece of glass. The technique is called polymer pen lithography.

The researchers grew MSCs on one type of nanoscopic sculpture, and were able to direct their developmental fate.

“Starting with millions of possibilities, we quickly zeroed in on the pattern of features that best directed the stem cells into osteocytes [bone cells],” says Chad A Mirkin, who led the work.

Mirkin is professor of chemistry in the Weinberg College of Arts and Sciences and is also the director of Northwestern’s International Institute for Nanotechnology.

The potential of this tool is to be able to take pluripotent stem cells from a patient, run them over a selected three-dimensional matrix in order to convert them rapidly into a particular cell type of choice, and then return them to the patient for repair and replenishment of damaged tissues.

“With further development, researchers might be able to use this approach to prepare cells of any lineage on command,” Mirkin says.

“The three-dimensional aspect is very interesting, and mimics aspects of the environment in a highly stylized way,” says Fiona Watt, professor and director of the Centre for Stem Cells and Regenerative Medicine at Kings College London.

“Several reports argue that the topology imposed on a stem cell – how a stem cell is contained in 3D – affects its behaviour. When you consider your bones and cartilage, this makes perfect sense,” Watt adds.

One important aspect of this work according to Marilyn Monk, emeritus professor of molecular embryology at University College London’s Institute of Child Health, is that it provides evidence that stem-cell fate can solely be informed by the local three-dimensional molecular structure.

“But that’s not to say that this is the only way to direct stem-cell fate,” Monk says. “We know that regulation of development involves multiple mechanisms that operate independently and inter-dependently to bring about a final specific cell function.”

Nonetheless he believes the technique is a real advance. “It would be neat to see if they can take a stem cell, already committed in one developmental direction, and back it up so that it might become another type of cell again, using only their patterning technique,” he says.

“That would be the Nobel prize.”

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Fighting Cancer and Drug Resistance – A ‘Nanosystem’ Does Both


Cancer is often referred to as “smart,” and this term often refers to the ability of these cells to proliferate without purpose or restraint.

The ability of cancer cells to develop multidrug resistance (MDR), a major problem that patients can face, making treatment against this disease even more elusive.

In an effort to combat both cancer cell proliferation and MDR, a recent study conducted by researchers from the National Health Research Institutes of Taiwan and the National Science Council of Taiwan have developed a nanosystem capable of addressing both challenges in the field of cancer therapy.

Drug Resistance and Cancer

Patients with several forms of blood cancer and solid tumors in the breast, ovaries, lungs and lower gastrointestinal tract can become untreatable as a result of multidrug resistance (MDR).

In MDR, the cancer cells of these patients become resistant to commonly used therapeutic drugs as a result of an overexpression of ATP-binding cassette (ABC) transporters that effectively push out drug molecules following administration.

P-glycoprotein and what is termed as the multidrug resistance-associated protein (MRP) are two of the most studied pumps present in cancer cells that are capable of rejecting chemotherapeutic drugs.

By avoiding the toxic effects of these drugs, cancer cells are able to continue to proliferate and metastasize to other organs of the body.

Unfortunately, some of the most commonly used cancer therapeutic drugs such as colchicine, vinblastine, doxorubicin, etoposide, paclitaxel, certain vinca alkaloids and other small molecules have shown resistance in various cancer cells.

Current research efforts in the field of anticancer drug discovery have looked towards the administration of combinatorial technology to be administered with cancer to effectively prevent cancer cells from physically removing therapeutic drugs when administered together.

While blocking the action of pumps like MRP and P-glycoprotein has shown some efficacy, transcription factors, such as c-Jun, which plays a role in cell, proliferation and MDR, can still potentiate metastasis.

Therefore, there remains a need to develop cancer therapies that work against drug resistance and simultaneously prevent further metastasis.

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The Efficacy of Administering Doxorubicin Mesoporous Silica Nanoparticles (MSNs)

Mesoporous silica nanoparticles (MSNs) are well-documented drug delivery vehicles that allow for a high drug loading capacity with minimal side effects upon administration.

The tunable size properties, thermal stability, photostability and ease of functionalization to different applications make MSNs one of the most promising options for therapeutic delivery systems.

In the recent study published in Nano Futures, the group of scientists led by Leu-Wei Lo covalently conjugated MSNs with doxorubicin and tested the ability of these nanosystems to be taken up by cancer cells in vitro.

The PC-3 cell line of metastatic human prostate carcinoma cells were treated with 100 μg/ml of either Dox-MSNs that were conjugated with DNAzyme, (Dox-MSN-Dz), Dox-MSNs or control MSNs for 24 hours to study the ability of these cells to survive following treatment.

The researchers found the Dox-MSN-Dz reduced cell survival rates by over 80%, whereas the Dox-MSNs alone still reduced cell survival rates by 60%.

The results of this study confirm the therapeutic potential of the developed multifunctional nanosystem, which incorporates doxorubicin, a widely used chemotherapeutic drug, MSNs and DNAzyme.

Not only did this nanosystem improve the cytotoxicity of doxorubicin to a resistance cancer cell line, but it also successfully reduced migration of cancer cells by inhibiting c-Jun.

While further in vivo studies need to be conducted to fully evaluate the ability of Dox-MSN-Dz to prevent metastasis and invade highly resistance cancer cells, the results of this study are promising.

Future research initiatives that incorporate different chemotherapeutic drugs into a similar nanosystem design could also show similar bifunctional properties as presented here.

Image Credit:

fusebulb/Shutterstock.com

References:

1 “A co-delivery nanosystem of chemotherapeutics and DNAzyme overcomes cancer drug resistance and metastasis” S. Sun, C. Liu, et al. Nano Futures. (2017). DOI: 10.1088/2399-1984/aa996f.

MIT: Researchers Develop Nanoparticles that Deliver the CRISPR genome-editing system – Big Step Forward for Cancer Research


In a new study, MIT researchers have developed nanoparticles that can deliver the CRISPR genome-editing system and specifically modify genes in mice.

The team used nanoparticles to carry the CRISPR components, eliminating the need to use viruses for delivery.

Using the new delivery technique, the researchers were able to cut out certain genes in about 80 percent of liver cells, the best success rate ever achieved with CRISPR in adult animals.

“What’s really exciting here is that we’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

One of the genes targeted in this study, known as Pcsk9, regulates cholesterol levels. Mutations in the human version of the gene are associated with a rare disorder called dominant familial hypercholesterolemia, and the FDA recently approved two antibody drugs that inhibit Pcsk9.

However these antibodies need to be taken regularly, and for the rest of the patient’s life, to provide therapy. The new nanoparticles permanently edit the gene following a single treatment, and the technique also offers promise for treating other liver disorders, according to the MIT team.

Anderson is the senior author of the study, which appears in the Nov. 13 issue of Nature Biotechnology. The paper’s lead author is Koch Institute research scientist Hao Yin.

Other authors include David H. Koch Institute Professor Robert Langer of MIT, professors Victor Koteliansky and Timofei Zatsepin of the Skolkovo Institute of Science and Technology, and Professor Wen Xue of the University of Massachusetts Medical School.

Targeting Disease

Many scientists are trying to develop safe and efficient ways to deliver the components needed for CRISPR, which consists of a DNA-cutting enzyme called Cas9 and a short RNA that guides the enzyme to a specific area of the genome, directing Cas9 where to make its cut.

In most cases, researchers rely on viruses to carry the gene for Cas9, as well as the RNA guide strand. In 2014, Anderson, Yin, and their colleagues developed a nonviral delivery system in the first-ever demonstration of curing a disease (the liver disorder tyrosinemia) with CRISPR in an adult animal. However, this type of delivery requires a high-pressure injection, a method that can also cause some damage to the liver.

Later, the researchers showed they could deliver the components without the high-pressure injection by packaging messenger RNA (mRNA) encoding Cas9 into a nanoparticle instead of a virus. Using this approach, in which the guide RNA was still delivered by a virus, the researchers were able to edit the target gene in about 6 percent of hepatocytes, which is enough to treat tyrosinemia.

While that delivery technique holds promise, in some situations it would be better to have a completely nonviral delivery system, Anderson says.

One consideration is that once a particular virus is used, the patient will develop antibodies to it, so it couldn’t be used again.

Also, some patients have pre-existing antibodies to the viruses being tested as CRISPR delivery vehicles.

In the new Nature Biotechnology paper, the researchers came up with a system that delivers both Cas9 and the RNA guide using nanoparticles, with no need for viruses.

To deliver the guide RNAs, they first had to chemically modify the RNA to protect it from enzymes in the body that would normally break it down before it could reach its destination.

The researchers analyzed the structure of the complex formed by Cas9 and the RNA guide, or sgRNA, to figure out which sections of the guide RNA strand could be chemically modified without interfering with the binding of the two molecules. Based on this analysis, they created and tested many possible combinations of modifications.

“We used the structure of the Cas9 and sgRNA complex as a guide and did tests to figure out we can modify as much as 70 percent of the guide RNA,” Yin says. “We could heavily modify it and not affect the binding of sgRNA and Cas9, and this enhanced modification really enhances activity.”

Reprogramming the Liver

The researchers packaged these modified RNA guides (which they call enhanced sgRNA) into lipid nanoparticles, which they had previously used to deliver other types of RNA to the liver, and injected them into mice along with nanoparticles containing mRNA that encodes Cas9.

They experimented with knocking out a few different genes expressed by hepatocytes, but focused most of their attention on the cholesterol-regulating Pcsk9 gene. The researchers were able to eliminate this gene in more than 80 percent of liver cells, and the Pcsk9 protein was undetectable in these mice. They also found a 35 percent drop in the total cholesterol levels of the treated mice.

The researchers are now working on identifying other liver diseases that might benefit from this approach, and advancing these approaches toward use in patients.

“I think having a fully synthetic nanoparticle that can specifically turn genes off could be a powerful tool not just for Pcsk9 but for other diseases as well,” Anderson says.

“The liver is a really important organ and also is a source of disease for many people. If you can reprogram the DNA of your liver while you’re still using it, we think there are many diseases that could be addressed.”

“We are very excited to see this new application of nanotechnology open new avenues for gene editing,” Langer adds.

Materials provided by MIT News.Note: Content may be edited for style and length. 

Metal-free nanoparticle could expand MRI use, tumor detection



What might sound like the set-up to a joke actually has a clinical answer: Both groups can face health risks when injected with metal-containing agents sometimes needed to enhance the color contrast — and diagnostic value — of MRIs.

But a new metal-free nanoparticle developed by the University of Nebraska-Lincoln and MIT could help circumvent these health- and age-related barriers to the powerful diagnostic tool, which physicians use to investigate or confirm a broad range of medical issues.

The team’s nanoparticle contains a non-metallic molecule that enhances MRI contrast to help distinguish among bodily tissue, a task typically performed by contrast agents containing gadolinium or other metals (ACS Central Science, “Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors”).

It also survived long enough to congregate around tumors in mice, suggesting the nanoparticle could help detect cancers as well as its metallic counterparts while eliminating concerns about the long-term accumulation of metal in the body.


MRIs of a mouse before (first and third rows) and 20 hours after being injected with a low dose (second row) and high dose (fourth row) of a new metal-free contrast agent developed by Nebraska and MIT. The yellow arrow indicates the location of a tumor. (click on image to enlarge)

Contrast in styles

The molecules residing in the team’s nanoparticle belong to a family known as the nitroxides, which are among the most promising alternatives to the metallic agents often injected into patients prior to undergoing MRIs.

But antioxidants in the body typically begin breaking down nitroxides within minutes, limiting how long they can enhance the contrast of an MRI. And the team’s molecule of interest — a so-called organic radical — has just a single electron, a fact that normally inhibits how much contrast it can produce.

Gadolinium and other metals possess multiple electrons that help them influence how the magnetic waves produced by an MRI interact with water molecules in tissue. This magnetic influence, or relaxivity, ultimately dictates the strength of contrast signals that get converted into the familiar multicolored MRIs.

So Nebraska chemist Andrzej Rajca began collaborating with colleagues at MIT to design a metal-free nanoparticle that would exhibit stability and relaxivity comparable to gadolinium’s. Rajca previously designed a nitroxide that, when embedded within relatively small nanoparticles, displayed a relaxivity several times greater than its predecessors.

This time around, MIT researchers incorporated Rajca’s nitroxide into a large nanoparticle known as a brush-arm star polymer. The process involved assembling polymers into a spherical structure with a water-attracting core and water-repelling shell, then squeezing multitudes of nitroxide molecules between that core and shell.

The team found that packing so many nitroxides into such tight quarters effectively multiplied their individual relaxivity values, resulting in a nanoparticle with a relaxivity about 40 times higher than a typical nitroxide.

“You don’t need much of the (new) contrast agent to see a good image,” said Rajca, Charles Bessey Professor of chemistry.

The nanoparticle’s polymer shell also helped slow the advance of the disruptive antioxidants enough to prolong the nitroxides’ lifespan from roughly two hours to 20. By injecting mice with their agent, the researchers showed that the nanoparticle’s longevity and large size allow it to reach tumors and differentiate them from normal tissue. Even in doses larger than those typically needed for MRIs, the team’s contrast agent showed no signs of toxicity in human cells or mice.

Source: University of Nebraska-Lincoln

Long-Term Health Monitoring Possible through Breathable, Wearable Electronics on Our Skin


Nano Skin breathablewe
The diagram at top illustrates the structure of gold nanomesh conductors laminated onto the skin surface. The nanomesh, constructed from polyvinyl alcohol (PVA) nanofibers and a gold (Au) layer, adheres to the skin when sprayed with water, …more

A hypoallergenic electronic sensor can be worn on the skin continuously for a week without discomfort, and is so light and thin that users forget they even have it on, says a Japanese group of scientists. The elastic electrode constructed of breathable nanoscale meshes holds promise for the development of noninvasive e-skin devices that can monitor a person’s health continuously over a long period.

Wearable electronics that monitor heart rate and other vital health signals have made headway in recent years, with next-generation gadgets employing lightweight, highly elastic materials attached directly onto the skin for more sensitive, precise measurements. However, although the  and rubber sheets used in these devices adhere and conform well to the skin, their lack of breathability is deemed unsafe for long-term use: dermatological tests show the fine, stretchable materials prevent sweating and block airflow around the skin, causing irritation and inflammation, which ultimately could lead to lasting physiological and psychological effects.

“We learned that devices that can be worn for a week or longer for continuous monitoring were needed for practical use in medical and sports applications,” says Professor Takao Someya at the University of Tokyo’s Graduate School of Engineering whose research group had previously developed an on-skin patch that measured oxygen in blood.

In the current research, the group developed an electrode constructed from nanoscale meshes containing a water-soluble polymer, polyvinyl alcohol (PVA), and a gold layer—materials considered safe and biologically compatible with the body. The  can be applied by spraying a tiny amount of water, which dissolves the PVA nanofibers and allows it to stick easily to the skin—it conformed seamlessly to curvilinear surfaces of human skin, such as sweat pores and the ridges of an index finger’s fingerprint pattern.

Breathable, wearable electronics on skin for long-term health monitoring
An array of nanomesh conductors attached to a fingertip, top, and a scanning electron microscope (SEM) image of a nanomesh conductor on a skin replica, bottom. Credit: 2017 Someya Laboratory.

The researchers next conducted a skin patch test on 20 subjects and detected no inflammation on the participants’  after they had worn the device for a week. The group also evaluated the permeability, with water vapor, of the nanomesh conductor—along with those of other substrates like ultrathin plastic foil and a thin rubber sheet—and found that its porous mesh structure exhibited superior gas permeability compared to that of the other materials.

Furthermore, the scientists proved the device’s mechanical durability through repeated bending and stretching, exceeding 10,000 times, of a conductor attached on the forefinger; they also established its reliability as an electrode for electromyogram recordings when its readings of the electrical activity of muscles were comparable to those obtained through conventional gel electrodes.

Breathable, wearable electronics on skin for long-term health monitoring
The electric current from a flexible battery placed near the knuckle flows through the conductor and powers the LED just below the fingernail. Credit: 2017 Someya Laboratory.

“It will become possible to monitor patients’ vital signs without causing any stress or discomfort,” says Someya about the future implications of the team’s research. In addition to nursing care and medical applications, the new device promises to enable continuous, precise monitoring of athletes’ physiological signals and bodily motion without impeding their training or performance.

 Explore further: Novel e-skin may monitor health, vital signs

More information: Akihito Miyamoto et al, Inflammation-free, gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes, Nature Nanotechnology (2017). DOI: 10.1038/nnano.2017.125

 

Nano Therapeutics to Nanobots ~ Nanotechnology is creating new opportunities for fighting disease (w/video)



Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Chemotherapy benefits a great many patients but the side effects can be brutal.


When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.


Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. 
At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”


In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

The researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “The main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?


Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world’s tiniest engine – just a few billionths of a metre in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

The forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the University’s commercialisation arm, the team in Cambridge’s Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

Source: By Sarah Collins, University of Cambridge

Rice University: Graphene Nanoribbons May Help Heal Damaged Spinal Cords: Dr. James M. Tour, PhD


rice-tour-diamond-damaged-spinal-cord-092016-newsimage_35057         
Rice University researchers James Tour, left, and William Sikkema. (Credit: Jeff Fitlow/Rice University)

Dr. James M. Tour, PhD (named among “The 50 Most Influential Scientists in the World Today” by TheBestSchools.org) at Rice University, stated that a treatment procedure to heal damaged spinal cords by combining graphene nanoribbons produced with a process invented at Rice and a common polymer is expected to gain importance.

As stated in an issue of Nature from 2009, chemists at the Tour lab started their research work with the discovery of a chemical process to unravel graphene nanoribbons from the multiwalled carbon nanotubes, and have been working with graphene nanoribbons for almost 10 years now.

Since then, the researchers have been using nanoribbons to produce better batteries, and improve materials for things such as, deicers for airplane wings and less-permeable containers that can store natural gas.

The recent research work by Rice University scientists has resulted in medical applications of nanoribbons. A material dubbed Texas-PEG has been developed that will help to treat damaged spinal cords or even knit severed spinal cords. Rice logo_rice3

A paper describing the results of preliminary animal-model tests has been published in the current issue of the journal Surgical Neurology International.

William Sikkema, a Rice graduate student and also a co-lead author of the paper has customized these graphene nanoribbons for use in the medical domain. This customized nanoribbon is highly soluble in polyethylene glycol (PEG), which is a biocompatible polymer gel that is generally used in pharmaceutical products, surgeries, and other biological applications.

While mixing biocompatible nanoribbons with PEG after the edges of these biocompatible nanoribbons are functionalized with PEG chains, an electrically active network that helps the damaged spinal cord to reconnect.

“Neurons grow nicely on graphene because it’s a conductive surface and it stimulates neuronal growth,” Tour said.

When studies were conducted at Rice University and at other places, it was observed that the neurons grew along with graphene.

We’re not the only lab that has demonstrated neurons growing on graphene in a petri dish. The difference is other labs are commonly experimenting with water-soluble graphene oxide, which is far less conductive than graphene, or nonribbonized structures of graphene. We’ve developed a way to add water-solubilizing polymer chains to the edges of our nanoribbons that preserves their conductivity while rendering them soluble, and we’re just now starting to see the potential for this in biomedical applications.

Dr. James M. Tour, PhD Chemist, Rice University
tourportrait2015-300

He also stated that ribbonized graphene structures allow smaller amounts to be utilized to preserve a conductive pathway to bridge the severed spinal cord. Tour explained that only 1% of Texas-PEG comprises of nanoribbons, and that is enough to build a conductive scaffold where the spinal cord can reconnect.

Co-authors Bae Hwan Lee and C-Yoon Kim conducted an experiment at Konkuk University in South Korea, and observed that Texas-PEG was successfully able to restore function in a rodent that had a severed spinal cord. Tour explained that the material provided reliable motor and sensory neuronal signals to pass through the gap for 24 hours after total transection of the spinal cord and nearly perfect motor control recovery after 14 days.

This is a major advance over previous work with PEG alone, which gave no recovery of sensory neuronal signals over the same period of time and only 10 percent motor control over four weeks.

Dr. James M. Tour, PhD Chemist, Rice University

The seed to start this project began when Sikkema came across a study undertaken by Italian neurosurgeon Sergio Canavero. Sikkema expected nanoribbons to enhance the research work that was based on PEG’s ability to promote the fusion of cell membranes by adding directional control for neurons and electrical conductivity while they spanned the gap between sections of the spinal cord. Developing contacts with the doctor resulted in a tie up with the South Korean researchers.

Tour told that Texas-PEG’s ability to help patients having spinal cord injuries is too reliable to be ignored. “Our goal is to develop this as a way to address spinal cord injury. We think we’re on the right path,” he said.

This is an exciting neurophysiological analysis following complete severance of a spinal cord. It is not a behavioral or locomotive study of the subsequent repair. The tangential singular locomotive analysis here is an intriguing marker, but it is not in a statistically significant set of animals. The next phases of the study will highlight the locomotive and behavioral skills with statistical relevance to assess whether these qualities follow the favorable neurophysiology that we recorded here.

Dr. James M. Tour, PhD Chemist, Rice University

Kim, co-primary author of the paper, is a research professor in the Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, South Korea, and a researcher at Seoul National University. Lee is an associate professor of physiology at the Yonsei University College of Medicine, Seoul. Tour is the T.T. and W.F. Chao Professor of Chemistry as well as a professor of computer science and of materials science and nanoengineering. Co-authors are In-Kyu Hwang of Konkuk University, Hanseul Oh of Seoul National University and Un Jeng Kim of the Yonsei University College of Medicine.

Source: http://www.rice.edu/

MIT: Seeking sustainable solutions through Nanotechnology – Engineer’s designs may help purify water, diagnose disease in remote regions of world.


mit-karnik-rohit-1“I try to guide my research by … asking myself the question, ‘What can we do today that will have a lasting impact and be conducive to a sustainable human civilization?’” says Rohit Karnik, an associate professor in MIT’s Department of Mechanical Engineering. Photo: Ken Richardson

In Rohit Karnik’s lab, researchers are searching for tiny solutions to some of the world’s biggest challenges.

In one of his many projects, Karnik, an associate professor in MIT’s Department of Mechanical Engineering, is developing a new microfluidic technology that can quickly and simply sorts cells from small samples of blood. The surface of a microfluidic channel is patterned to direct certain cells to roll toward a reservoir for further analysis, while allowing the rest of the blood sample to pass through. With this design, Karnik envisions developing portable, disposable devices that doctors may use, even in remote regions of the world, to quickly diagnose conditions ranging from malaria to sepsis.

Karnik’s group is also tackling issues of water purification. The researchers are designing filters from single layers of graphene, which are atom-thin sheets of carbon known for their exceptional strength. Karnik has devised a way to control the size and concentration of pores in graphene, and is tailoring single layers to filter out miniscule and otherwise evasive contaminants. The group has also successfully filtered salts using the technique and hopes to develop efficient graphene filters for water purification and other applications. Silver Nano P clean-drinking-water-india

In looking for water-purifying solutions, Karnik’s group also identified a surprisingly low-tech option: the simple tree branch. Karnik found that the pores within a pine branch that normally help to transport water up the plant are ideal for filtering bacteria from water. The group has shown that a peeled pine branch can filter out up to 99.00 percent of E. coli from contaminated water. Karnik’s group is building up on this work to explore the potential for simple and affordable wood-based water purification systems.

“I try to guide my research by long-term sustainability, in a specific sense, by asking myself the question, ‘What can we do today that will have a lasting impact and be conducive to a sustainable human civilization?’ Karnik says. “I try to align myself with that goal.”

From stargazer to tinkerer

Karnik was born and raised in Pune, India, which was then a relatively quiet city 100 miles east of Mumbai. Karnik describes himself while growing up as shy, yet curious about the way the world worked. He would often set up simple experiments in his backyard, seeing, for instance, how transplanting ants from one colony to another would change the ants’ behavior. (The short answer: They fought, sometimes to the death.) He developed an interest in astronomy early on and often explored the night sky with a small telescope, from the roof of his family’s home.

“I used to take my telescope up to the terrace in the middle of the night, which required three different trips up six or seven flights of stairs,” Karnik says. “I’d set the alarm for 3 a.m., go up, and do quite a bit of stargazing.”

That telescope would soon serve another use, as Karnik eventually found that, by inverting it and adding another lens, he could repurpose the telescope as a microscope.

“I built a little setup so I could look at different things, and I used to collect stuff from around the house, like onion peels or fungus growing on trees, to look at their cells,” Karnik says.

When it came time to decide on a path of study, Karnik was inspired by his uncle, a mechanical engineer who built custom machines “that did all kinds of things, from making concrete bricks, to winding up springs,” Karnik says. “What I saw in mechanical engineering was the ability to building something that integrates across different disciplines.”

Seeking balance and insight

As an entering student at the Indian Institute of Technology Bombay, Karnik chose to study mechanical engineering over electrical engineering, which was the more popular choice among students at the time. For his thesis, he looked for new ways to model three-dimensional cracks in materials such as steel beams.

Casting around for a direction after graduating, Karnik landed on the fast-growing field of nanotechnology. Arun Majumdar, an IIT alum and professor at the University of California at Berkeley, was studying energy conversion and biosensing in nanoscale systems. Karnik joined the professor’s lab as a graduate student, moving to California in 2002. For his graduate work, Karnik helped to develop a microfluidic platform to rapidly mix the contents of and test reactions occurring within droplets. He followed this work up with a PhD thesis in which he explored how fluid, flowing through tiny, nanometer-sized channels, can be controlled  to sense and direct ions and molecules.

Toward the end of his graduate work, Karnik interviewed for and ultimately accepted a faculty position at MIT. However, he was still completing his PhD thesis at Berkeley and had less than 4 years of experience beyond his bachelor’s degree. To help ease the transition, MIT offered Karnik an interim postdoc position in the lab of Robert Langer, the David H. Koch Institute Professor and a member of the Koch Institute for Integrative Cancer Research.

“It was an insightful experience,” Karnik remembers. “For a mechanical engineer who’s never been outside mechanical engineering, I basically had little experience how to do things in biology. It opened up possibilities for working with the biomedical community.”

When Karnik finally assumed his position as assistant professor of mechanical engineering in 2007, he experienced a tidal wave of deadlines, demands, and responsibilities — a common initiation for first-time faculty.

“By its nature the job is overwhelming,” Karnik says. “The trick is how to maintain balance and sanity and do the things you like, without being distracted by the busyness around you, in some sense.”

He says several things have helped him to handle and even do away with stress: walks, which he takes each day to work and around campus, as well as yoga and meditation.

“If you can see things the way they are, by clearing away the filters your mind puts in place, you can get a clear perspective, and there are a lot of insights that come through,” Karnik says.

U of California: Nano submarines could change healthcare, says nanoengineer professor


Nano Subs 082316 1471860105809A leading global chemist has come to the Sunshine Coast to discuss how his team is close to creating a successful nano submarine that could revolutionise the healthcare system.

When asked what exactly a “nano submarine” was, University of California San Diego chair of nanoengineering professor Joseph Wang described it as like something taken from the 1966 film Fantastic Voyage, where medical personnel board a submarine were shrunk to microscopic size to travel through the bloodstream of a wounded diplomat and save his life.

Professor Wang said his team was getting closer to the goal of using nano submarines in a variety of ways, minus the shrunken humans and sabotage of the 1966 film.

“It’s like the Fantastic Voyage movie, where you want to improve therapeutic and diagnostic abilities through proper timing and proper location to improve efficiency,” he said.

“It is like shrinking a big submarine a million times to get the nano-scale submarine.

“We use special nano fabrications to create it.

“You can call it submarine or a nano machine, there are different names for it.”

One nanometer is one-billionth of a meter. To put this into perspective, a strand of human DNA is 2.5 nanometers in diameter while a sheet of paper is about 100,000 nanometers thick.Nano Subs 061416 untitled

Professor Wang said the nano submarines could be tailored to specific applications, including diagnosis, treatment and imaging and would use energy within the body’s system to generate its movement.

“It is powered by the blood, by chemical in the blood like glucose, it can autonomously move in blood,” he said.

“This is all part of what we call nano medicine, precision medicine that we use to improve medicines.

“It could improve imaging, diagnosis, treatment, it is multifunctional.”

Professor Wang said there was a fair way to go before human testing could begin, but said the pioneering work could improve drug treatments by providing a more targeted approach.

“Compared to (current) drug delivery, it could take cargo, the drug, and dispose it at the right location, right time and could improve the efficiency of drug,” he said.

Professor Wang was presenting a free public seminar on nano submarines at University of Sunshine Coast’s Innovation Centre at Sippy Downs.

 

Nanoparticles that Speed Blood Clotting ~ Great Things from Small Things ~ May One Day Save Lives


Blood Clot NPs 082216 10-nanoparticle.jpgNanoparticles (green) help form clots in an injured liver. The researchers added color to the scanning electron microscopy image after it was taken. Credit: Erin Lavik, Ph.D.

Whether severe trauma occurs on the battlefield or the highway, saving lives often comes down to stopping the bleeding as quickly as possible. Many methods for controlling external bleeding exist, but at this point, only surgery can halt blood loss inside the body from injury to internal organs.

Now, researchers have developed nanoparticles that congregate wherever injury occurs in the body to help it form blood clots, and they’ve validated these particles in test tubes and in vivo.

The researchers will present their work today at the 252nd National Meeting & Exposition of the American Chemical Society (ACS).

“When you have uncontrolled internal bleeding, that’s when these particles could really make a difference,” says Erin B. Lavik, Sc.D. “Compared to injuries that aren’t treated with the nanoparticles, we can cut bleeding time in half and reduce total .”

Trauma remains a top killer of children and younger adults, and doctors have few options for treating internal bleeding. To address this great need, Lavik’s team developed a nanoparticle that acts as a bridge, binding to activated platelets and helping them join together to form clots. To do this, the nanoparticle is decorated with a molecule that sticks to a glycoprotein found only on the activated platelets.

Nano Body II 43a262816377a448922f9811e069be13Initial studies suggested that the nanoparticles, delivered intravenously, helped keep rodents from bleeding out due to brain and spinal , Lavik says. But, she acknowledges, there was still one key question: “If you are a rodent, we can save your life, but will it be safe for humans?”

As a step toward assessing whether their approach would be safe in humans, they tested the immune response toward the particles in pig’s blood. If a treatment triggers an immune response, it would indicate that the body is mounting a defense against the nanoparticle and that side effects are likely. The team added their nanoparticles to pig’s blood and watched for an uptick in complement, a key indicator of immune activation. The particles triggered complement in this experiment, so the researchers set out to engineer around the problem.

“We made a battery of particles with different charges and tested to see which ones didn’t have this immune-response effect,” Lavik explains. “The best ones had a neutral charge.” But neutral nanoparticles had their own problems. Without repulsive charge-charge interactions, the nanoparticles have a propensity to aggregate even before being injected. To fix this issue, the researchers tweaked their nanoparticle storage solution, adding a slippery polymer to keep the nanoparticles from sticking to each other.

Lavik also developed nanoparticles that are stable at higher temperatures, up to 50 degrees Celsius (122 degrees Fahrenheit). This would allow the particles to be stored in a hot ambulance or on a sweltering .

In future studies, the will test whether the new particles activate complement in human blood. Lavik also plans to identify additional critical safety studies they can perform to move the research forward. For example, the team needs to be sure that the do not cause non-specific clotting, which could lead to a stroke. Lavik is hopeful though that they could develop a useful clinical product in the next five to 10 years.

Explore further: Researchers take the inside route to halt bleeding

More information: Engineering nanoparticles to stop internal bleeding, 252nd National Meeting & Exposition of the American Chemical Society (ACS), 2016.

Abstract
Young people between 5 and 44 are most likely to die from a trauma, and the primary cause of death will be bleeding out. We have a range of technologies to control external bleeding, but there is a dearth of technologies for internal bleeding.
Following injury, platelets become activated at the injury site.

We have designed nanoparticles that are administered intravenously that bind with activated platelets to help form platelet plugs more rapidly. We have investigated the behavior of these particles in an number of in vitro systems to understand their behavior. We have also tested these particles in a number of models of trauma. The particles lead to a reduction in bleeding in a number of models of trauma including models of brain and spinal cord injury, and these particles lead to increased survival.
This work is not without challenges. One of the goals is to be able to use these particles in places where there are extreme temperatures and storage is challenging. We have engineering a variant of the hemostatic nanoparticles that is stable up to 50 C. A second challenge is that the intravenous administration of nanoparticles triggers complement activation as has been seen in a wide range of nanoparticle technologies from DOXIL to imaging agents.

The solution is generally to administer the particles very slowly to modulate the physiological responses to complement activation, but that is not an option when one is bleeding out, so we have had to develop variants that reduce complement activation and the accompanying complications.
Ultimately, we hope that this work provides insight and, potentially, a new approach to dealing with internal bleeding.