Injectable nanoparticles show ‘astounding’ prowess against cancer


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Latest Nanotechnology Fights Hard-to-Treat Tumors

The most difficult to treat and deadly of cancers may have met their match. Nanotechnology, at the forefront of cancer research, now has a new application, Medical News Today reports.

Mauro Ferrari, president and CEO of the Houston Methodist Research Institute in Texas, has found a way to inject metastatic tumors with nanoparticles, releasing cancer-fighting drugs directly into the tumors themselves.

Existing cancer drugs are limited in the fight against tumors in areas like the lungs and liver because of the body’s protective biological barriers. Basically, the cancer fighting drugs fail to reach their intended targets and wind up damaging healthy tissues.

“This may sound like science fiction, like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational,” Ferrari tells Medical News Today. “I would never want to over-promise to the thousands of cancer patients looking for a cure, but the data is astounding.

“We’re talking about changing the landscape of curing metastatic disease, so it’s no longer a death sentence.”

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A few decades ago, the idea of developing any type of solution in the nanoscale was nothing more than a dream.

The word “nanotechnology” was only seen in print for the first time as recently as 1986.

Manipulating, creating and utilizing objects that are 100,000 times smaller than the width of a hair is science fiction turned science fact.

Today, nano-sized particles help golf balls fly straighter, make the surfaces of bowling balls more durable and give exterior varnishes a longer life.

Industry and manufacturing have taken nanoparticles to their bosom, but their abilities are also being tested for possible uses in the medical sphere; for instance, bandages infused with silver nanoparticles have been designed to help wounds heal faster.

Among the list of potential medical uses for nanotechnology are targeted drug delivery systems in the fight against diseases, including cancer.

Current cancer drug delivery

Metastases of cancers in the lung and liver are the primary causes of cancer deaths. In many cases, existing cancer drugs are of limited power because of the body’s protective biological barriers. The chemicals fail to reach their intended targets in high enough concentrations and are distributed into healthy tissues, causing serious side effects.

Mauro Ferrari, president and CEO of the Houston Methodist Research Institute in Texas, has been working with nanomedicine for 20 years, and his latest research provides some of the most impressive results to date.

Ferrari and his team created a mechanism by which nanoparticles could move through these biological defenses and, once inside the tumor, release the toxic chemicals directly into the heart of the problem.

Injectable nanoparticle generator

Cancer shapeshiftinThe team used an injectable nanoparticle generator (iNPG), composed of the active drug – doxorubicin – packaged as thin strands of polymer within a nanoporous silicon material.

Once the iNPG enters the tumor, the silicon outer coating naturally degrades, releasing the polymer strands. The strands curl up into nano-scale balls and enter the cancer cells themselves. As the balls move freely around the cell and approach the nucleus, the pH becomes more acidic. This drop in pH triggers the strands to release the doxorubicin, which then kills the cell.

The iNPGs were trialed on mice with triple negative breast cancer that had metastasized into the tissues of the lungs. Triple negative cancers account for roughly 1 in 10 breast cancers. They are particularly difficult to treat and do not respond to hormonal therapy.

‘What we discovered is transformational’

Although the prognosis for triple negative cancer is poor, Ferrari and his team found that 50% of the mice treated by the iNPGs showed no traces of metastatic disease after an 8-month period, which is considered the equivalent of 24 human years.

Ferrari says:

“This may sound like science fiction, like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational. We invented a method that actually makes the nanoparticles inside the cancer and releases the drug particles at the site of the cellular nucleus.”

The investigators are incredibly pleased with these results and hope they will shepherd in a new dawn of medical intervention. Any headway into the treatment of such an intractable disease is entirely welcome.

The authors say that “with this injectable nanoparticle generator, we were able to do what standard chemotherapy drugs, vaccines, radiation and other nanoparticles have all failed to do.” The Houston Methodist Research Institute are hoping to fast-track the research and secure FDA (US Food and Drug Administration) approval as soon as possible. They plan to trial the drugs in humans in 2017.

Although keen to keep the findings in perspective and not raise hopes unnecessarily, Ferrari has a difficult time keeping his positivity under wraps:

“I would never want to over-promise to the thousands of cancer patients looking for a cure, but the data is astounding. We’re talking about changing the landscape of curing metastatic disease, so it’s no longer a death sentence.”

Ferrari’s excitement is both palpable and understandable. Even if future research using human participants returns with survival rates that are only a fraction of those found in the present study, the results will be deemed a rousing success.

Medical News Today recently covered news of another “groundbreaking” cancer discovery that holds promise for personalizing cancer therapy.

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How Nanotechnology is Poised to Change Medicine Forever


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*** Re-Posted from “Big Think”

Science fiction movies such as Ant-Man and Fantastic Voyage excite us about the possibility of shrinking ourselves down to the subatomic level. In the Disney version of The Sword in the Stone, Merlin defeats the sorceress Madam Mim in a shape shifting battle by turning into a microbe which makes her sick. All of these touch upon the power that comes with being able to control what is infinitesimally small. In reality, science has made great progress in this regard. But we’re not quite there yet. The prefix nano comes from ancient Greek meaning, “dwarf.” Mathematically speaking, it refers to one billionth of a unit of measure. For instance, a nanometer (nm) equals one billionth of a meter (0.000000001 meters). This is 40,000 times smaller than the width of a human hair, or around three to five atoms wide.

Nanotechnology is the ability to control and manipulate matter on the atomic or molecular level. This new branch of technology is already being used, albeit passively, in sunscreens and cosmetics. But future applications promise so much more. Nanotech could have a revolutionary impact on diagnostics, research, development, drug delivery, tissue repair, detox, surgery, health monitoring, and gene therapy, among other places. Consider a lab working on the subatomic level, able to create microscopic robots and tools to deliver medicines, manipulate the components of a cell, and piece together or take apart DNA. All of this may someday be commonplace in hospitals, labs, and medical centers. Right now, this technology is in its seminal stages, slowly transitioning from the realm of science fiction to science fact.

Possible uses of nanotech.

Nanotech could theoretically stretch DNA out like a bundle of wires. The nanobots would carry out repairs, or snip out faulty genes and replace them with healthy ones. This might someday make hereditary conditions obsolete. In 2004, New York University (NYU) chemists were able to create a nanobot from fragments of DNA able to walk on two legs, each a mere 10 nanometers long. This “nanowalker” could take two steps forward or back. Ned Seeman was one of the researchers on this project. He believes someday that a molecular scale assembly line could be fashioned. A molecule could be moved along and put into place by nanobots in order to engage certain health effects.

Nanobots are also being used to fight cancer. Harvard Medical School scientists recently reported an “origami nanorobot” comprised of DNA. Researchers successfully displayed how these could be used to deliver deadly molecules to lymphoma and leukemia cells, causing them to commit suicide. At Northwestern University nanostars have been developed. These are star shaped nanobots able to deliver drugs directly to cancer cells. Researchers showed that they could dispatch such drugs directly to the nuclei of ovarian and cervical cancer cells. The body often breaks down such drugs before they can be delivered. Nanostars may someday overcome this problem.

Different shapes of nanotech currently proposed.

Now consider “nanofactories.” Researchers at MIT showed how self-assembling proteins could deliver drugs directly to problem areas. So far, tests have been successful in laboratory mice, where nanoparticles released a specific protein when exposed to UV light. This may prove useful in fighting metastatic tumors, or those who send cancer cells to invade other organs and tissues, causing the cancer to spread. Metastatic disease is responsible for over 90% of all cancer deaths.

Nanofibers are another innovation coming down the pike. These are 1,000 nanometers or less in diameter. They might serve as components to artificial organs or tissues, surgical textiles, and even the next generation of wound dressings. Another area of promise is medical imaging. Nanoparticles could be used to achieve more precise imaging, aiding diagnostics and guiding surgeons. Matthew MacEwan, of the Washington University School of Medicine in St. Louis, has launched his own nanofiber company. These fibers can be used to repair bone, soft tissue, nerves, and even spinal cord and brain tissue in the wake of a debilitating injury.

Japanese researcher holding nanofiber sheet.

Though these possible innovations in nanotech sound wondrous, there are still many challenges ahead. Being a cutting-edge technology, the cost is high, limiting research and the ability to scale up production. This causes timetables to be stretched much farther out. A segment of the public is also wary of nanobots swimming around in their systems. Some are worried that the small size may cause complications, though there is no indication thus far that this technology is at all dangerous.

In fact, most researchers in the field say these particles are less toxic than your average household cleaning product. Nanoparticles are simply a part of nature. Theoretically however, if they do end up in the wrong part of the body or malfunction, they might cause disease instead of alleviating it. Then there are more ghastly fears. Could nanotech create robots which enter our brains and cause us to comply with government wishes, a new kind of 1984? Might it lead to an undetectable weapon able to propagate a new kind of terrorism? For now, these fears remain in the realm of science fiction. Whether or not future innovations allow these possibilities to surface is still up for debate. Today, the cost is too great for such worries to materialize, even on the molecular level.

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Rice De-icer Graphene Nano Ribbons gains anti-icing properties


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Rice University scientists have modified their graphene-based de-icer to resist the formation of ice well below the freezing point and added superhydrophobic capabilities. The robust film is intended for use in extreme environments as well …more

Rice University scientists have modified their graphene-based de-icer to resist the formation of ice well below the freezing point and added superhydrophobic capabilities. The robust film is intended for use in extreme environments as well …more
Rice University scientists have advanced their graphene-based de-icer to serve a dual purpose. The new material still melts ice from wings and wires when conditions get too cold. But if the air is above 7 degrees Fahrenheit, ice won’t form at all.

 

 

The Rice lab of chemist James Tour gave its de-icer superhydrophobic (water-repelling) capabilities that passively prevent water from freezing above 7 degrees. The tough film that forms when the de-icer is sprayed on a surface is made of atom-thin graphene nanoribbons that are conductive, so the material can also be heated with electricity to melt ice and snow in colder conditions.
The material can be spray-coated, making it suitable for large applications like aircraft, power lines, radar domes and ships, according to the researchers. The study was published this month in the American Chemical Society journal ACS Applied Materials and Interfaces.

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“We’ve learned to make an ice-resistant material for milder conditions in which heating isn’t even necessary, but having the option is useful,” Tour said. “What we now have is a very thin, robust coating that can keep large areas free of ice and snow in a wide range of conditions.”
Tour, lead authors Tuo Wang, a Rice graduate student, and Yonghao Zheng, a Rice postdoctoral researcher, and their colleagues tested the film on glass and plastic.
Rice de-icer gains anti-icing properties.

 
Test samples show a graphene nanoribbon-based film developed at Rice University with both passive and active de-icing properties. When the film at left is heated without an application of lubricants, ice melts but water droplets remain on …more
Materials are superhydrophobic if they have a water-contact angle larger than 150 degrees.

The term refers to the angle at which the surface of the water meets the surface of the material. The greater the beading, the higher the angle. An angle of 0 degrees is basically a puddle, while a maximum angle of 180 degrees defines a sphere just touching the surface.
The Rice films use graphene nanoribbons modified with a fluorine compound to enhance their hydrophobicity. They found that nanoribbons modified with longer perfluorinated chains resulted in films with a higher contact angle, suggesting that the films are tunable for particular conditions, Tour said. Warming test surfaces to room temperature and cooling again had no effect on the film’s properties, he said.

 
The researchers discovered that below 7 degrees, water would condense within the structure’s pores, causing the surface to lose both its superhydrophobic and ice-phobic properties. At that point, applying at least 12 volts of electricity warmed them enough to retain its repellant properties.

 
Applying 40 volts to the film brought it to room temperature, even if the ambient temperature was 25 degrees below zero. Ice allowed to form at that temperature melted after 90 seconds of resistive heating.

 
The researchers found that while effective, the de-icing mode did not remove water completely, as some remained trapped in the pores between linked nanoribbon bundles. Adding a lubricant with a low melting point (minus 61 degrees F) to the film made the surface slippery, sped de-icing and saved energy.

 

 

 
Explore further: Graphene nanoribbons an ice-melting coat for radar
More information: Tuo Wang et al, Passive Anti-icing and Active Deicing Films, ACS Applied Materials & Interfaces (2016). DOI: 10.1021/acsami.6b03060
Journal reference: ACS Applied Materials and Interfaces
Provided by: Rice University

 

MIT: Light can “heal” defects in some solar cells


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A sample of the mineral perovskite is shown in the foreground, while behind it is an image the researchers used to prove the effects of intense light on a thin film of perovskite. Fluorescence imaging shows that areas that received more light became more purified, as revealed by brighter fluorescence from those regions.

Image: MIT News. Fluorescence image courtesy of the researchers.

Defects in some new electronic materials can be removed by making ions move under illumination.

A family of compounds known as perovskites, which can be made into thin films with many promising electronic and optical properties, has been a hot research topic in recent years. But although these materials could potentially be highly useful in applications such as solar cells, some limitations still hamper their efficiency and consistency.

Now, a team of researchers at MIT and elsewhere say they have made significant inroads toward understanding a process for improving perovskites’ performance, by modifying the material using intense light. The new findings are being reported in the journal Nature Communications, in a paper by Samuel Stranks, a researcher at MIT; Vladimir Bulović, the Fariborz Maseeh (1990) Professor of Emerging Technology and associate dean for innovation; and eight colleagues at other institutions in the U.S. and the U.K. The work is part of a major research effort on perovskite materials being led by Stranks, within MIT’s Organic and Nanostructured Electronics Laboratory.

Tiny defects in perovskite’s crystalline structure can hamper the conversion of light into electricity in a solar cell, but “what we’re finding is that there are some defects that can be healed under light,” says Stranks, who is a Marie Curie Fellow jointly at MIT and Cambridge University in the U.K. The tiny defects, called traps, can cause electrons to recombine with atoms before the electrons can reach a place in the crystal where their motion can be harnessed.

Under intense illumination, the researchers found that iodide ions — atoms stripped of an electron so they carry an electric charge — migrated away from the illuminated region, and in the process apparently swept away most of the defects in that region along with them.

“This is the first time this has been shown,” Stranks says, “where just under illumination, where no [electric or magnetic] field has been applied, we see this ion migration that helps to clean the film. It reduces the defect density.”While the effect had been observed before, this work is the first to show that the improvement was caused by the ions moving as a result of the illumination.

This work is focused on particular types of the material, known as organic-inorganic metal halide perovskites, which are considered promising for applications including solar cells, light-emitting diodes (LEDs), lasers, and light detectors. They excel in a property called the photoluminescence quantum efficiency, which is key to maximizing the efficiency of solar cells. But in practice, the performance of different batches of these materials, or even different spots on the same film, has been highly variable and unpredictable. The new work was aimed at figuring out what caused these discrepancies and how to reduce or eliminate them.

Stranks explains that “the ultimate aim is to make defect-free films,” and the resulting improvements in efficiency could also be useful for applications in light emission as well as light capture.

Previous work reducing defects in thin-film perovskite materials has focused on electrical or chemical treatments, but “we find we can do the same with light,” Stranks says. One advantage of that is that the same technique used to improve the material’s properties can at the same time be used as a sensitive probe to observe and better understand the behavior of these promising materials.

Another advantage of this light-based processing is it doesn’t require anything to come in physical contact with the film being treated — for example, there is no need to attach electrical contacts or to bathe the material in a chemical solution. Instead, the treatment can simply be applied by turning on the source of illumination. The process, which they call photo-induced cleaning, could be “a way forward” for the development of useful perovskite-based devices, Stranks says.

The effects of the illumination tend to diminish over time, Stranks says, so “the challenge now is to maintain the effect” long enough to make it practical. Some forms of perovskites are already “looking to be commercialized by next year,” he says, and this research “raises questions that need to be addressed, but it also shows there are ways to address” the phenomena that have been limiting this material’s performance.

“I think the paper provides valuable insight that is likely to help people make more efficient solar cells by figuring out how to reduce the number of iodine vacancies,” says Michael McGehee, a professor of materials science and engineering at Stanford University, who was not involved in this research. “I think it is fascinating that illuminating the perovskites improves their photoluminescence efficiency by enabling iodine to move around and eliminate iodine vacancies. … This research does not make solar cells better, but it does greatly increase our understanding of how these complex materials function in solar cells.”

In addition to Stranks and Bulović, the team included Anna Osherov of MIT, Dane deQuilettes, Daniel Graham, and David Ginger of the University of Washington, and Wei Zhang, Victor Burlakov, Tomas Leitjens, and Henry Snaith of Oxford University in the U.K. The work was supported by the European Union Seventh Framework Programme, the U.S. National Science Foundation, the Center for Excitonics, an Energy Frontier Research Center at MIT funded by the U.S. Department of Energy, and the National Institutes of Health. 

MIT: Hot new solar cell System converts solar heat into usable light, increasing device’s overall efficiency


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While all research in traditional photovoltaics faces the same underlying theoretical limitations, MIT PhD student David Bierman says, “with solar thermal photovoltaics you have the possibility to exceed that.” In fact, theory predicts that in principle this method could more than double the theoretical limit of efficiency, potentially making it possible to deliver twice as much power from a given area of panels.

Photo courtesy of the researchers.

A team of MIT researchers has for the first time demonstrated a device based on a method that enables solar cells to break through a theoretically predicted ceiling on how much sunlight they can convert into electricity.

Ever since 1961 it has been known that there is an absolute theoretical limit, called the Shockley-Queisser Limit, to how efficient traditional solar cells can be in their energy conversion. For a single-layer cell made of silicon — the type used for the vast majority of today’s solar panels — that upper limit is about 32 percent. But it has also been known that there are some possible avenues to increase that overall efficiency, such as by using multiple layers of cells, a method that is being widely studied, or by converting the sunlight first to heat before generating electrical power. It is the latter method, using devices known as solar thermophotovoltaics, or STPVs, that the team has now demonstrated.

The findings are reported this week in the journal Nature Energy, in a paper by MIT doctoral student David Bierman, professors Evelyn Wang and Marin Soljačić, and four others.

While all research in traditional photovoltaics faces the same underlying theoretical limitations, Bierman says, “with solar thermophotovoltaics you have the possibility to exceed that.” In fact, theory predicts that in principle this method, which involves pairing conventional solar cells with added layers of high-tech materials, could more than double the theoretical limit of efficiency, potentially making it possible to deliver twice as much power from a given area of panels.

“We believe that this new work is an exciting advancement in the field,” Wang says, “as we have demonstrated, for the first time, an STPV device that has a higher solar-to-electrical conversion efficiency compared to that of the underlying PV cell.” In the demonstration, the team used a relatively low-efficiency PV cell, so the overall efficiency of the system was only 6.8 percent, but it clearly showed, in direct comparisons, the improvement enabled by the STPV system.

The basic principle is simple: Instead of dissipating unusable solar energy as heat in the solar cell, all of the energy and heat is first absorbed by an intermediate component, to temperatures that would allow that component to emit thermal radiation. By tuning the materials and configuration of these added layers, it’s possible to emit that radiation in the form of just the right wavelengths of light for the solar cell to capture. This improves the efficiency and reduces the heat generated in the solar cell.

The key is using high-tech materials called nanophotonic crystals, which can be made to emit precisely determined wavelengths of light when heated. In this test, the nanophotonic crystals are integrated into a system with vertically aligned carbon nanotubes, and operate at a high temperature of 1,000 degrees Celsius. Once heated, the nanophotonic crystals continue to emit a narrow band of wavelengths of light that precisely matches the band that an adjacent photovoltaic cell can capture and convert to an electric current. “The carbon nanotubes are virtually a perfect absorber over the entire color spectrum,” Bierman says, allowing it to capture the full solar spectrum. “All of the energy of the photons gets converted to heat.” Then, that heat gets re-emitted as light but, thanks to the nanophotonic structure, is converted to just the colors that match the PV cell’s peak efficiency.

In operation, this approach would use a conventional solar-concentrating system, with lenses or mirrors that focus the sunlight, to maintain the high temperature. An additional component, an advanced optical filter, lets through all the desired wavelengths of light to the PV cell, while reflecting back any unwanted wavelengths, since even this advanced material is not perfect in limiting its emissions. The reflected wavelengths then get re-absorbed, helping to maintain the heat of the photonic crystal.

Bierman says that such a system could offer a number of advantages over conventional photovoltaics, whether based on silicon or other materials. For one thing, the fact that the photonic device is producing emissions based on heat rather than light means it would be unaffected by brief changes in the environment, such as clouds passing in front of the sun. In fact, if coupled with a thermal storage system, it could in principle provide a way to make use of solar power on an around-the-clock basis. “For me, the biggest advantage is the promise of continuous on-demand power,” he says.

In addition, because of the way the system harnesses energy that would otherwise be wasted as heat, it can reduce excessive heat generation that can damage some solar-concentrating systems.

To prove the method worked, the team ran tests using a photovoltaic cell with the STPV components, first under direct sunlight and then with the sun completely blocked so that only the secondary light emissions from the photonic crystal were illuminating the cell. The results showed that the actual performance matched the predicted improvements.

“A lot of the work thus far in this field has been proof-of-concept demonstrations,” Bierman says. “This is the first time we’ve actually put something between the sun and the PV cell to prove the efficiency” of the thermal system. Even with this relatively simple early-stage demonstration, Bierman says, “we showed that just with our own unoptimized geometry, we in fact could break the Shockley-Queisser limit.” In principle, such a system could reach efficiencies greater than that of an ideal solar cell.

The next steps include finding ways to make larger versions of the small, laboratory-scale experimental unit, and developing ways of manufacturing such systems economically.

This represents a “significant experimental advance,” says Peter Bermel, an assistant professor of electrical and computer engineering at Purdue University, who was not associated with this work. “To the best of my knowledge, this is a new record for solar TPV, using a solar simulator, selective absorber, selective filter, and photovoltaic receiver, that reasonably represents actual performance that might be achievable outdoors.” He adds, “It also shows that solar TPV can exceed PV output with a direct comparison of the same cells, for a sufficiently high input power density, lending this approach to applications using concentrated sunlight.”

The research team also included MIT alumnus Andrej Lenert PhD ’14, now a research fellow at the University of Michigan, MIT postdocs Walker Chan and Bikram Bhatia, and research scientist Ivan Celanovic. The work was supported by the Solid-State Solar Thermal Energy Conversion (S3TEC) Center, funded by the U.S. Department of Energy.

Tiny packages may pack powerful treatment for brain tumors: Nanocarrier provides efficient delivery of chemotherapeutic drug


Brain Tumor 052416 160521071206_1_540x360Dr. Ann-Marie Broome, right, likes collaborating with Dr. Amy Lee Bredlau, left, who brings a clincial perspective to the laboratory.
Credit: Sarah Pack

Medical University of South Carolina: Great discoveries do come in small packages. Few know that better than Ann-Marie Broome, Ph.D., who feels nanotechnology holds the future of medicine with its ability to deliver powerful drugs in tiny, designer packages.

Her latest research finds the perfect application — targeting cancerous brain tumor cells.

Results from her recent paper published online in the international journal Nanomedicine — Future Medicine found that a lipid nanocarrier engineered to be small enough to get past the blood-brain barrier could be targeted to deliver a chemotherapeutic drug more efficiently to tumor cells in the brain. In vivo studies showed specific uptake and increased killing in glial cells, so much so that Broome initially questioned the results.

“I was very surprised by how efficiently and well it worked once we got the nanocarrier to those cells,” she said, explaining that initial results were so promising that she had her team keep repeating the experiments, using different cell lines, dosage amounts and treatment times.Researchers and clinicians are excited because it potentially points the way to a new treatment option for patients with certain conditions, such as glioblastoma multiforme (GBM), the focus of this study.

Glioblastoma multiforme is a devastating disease with no curative options due to several challenges, said Broome, who is the director of Molecular Imaging of the Medical University of South Carolina’s Center for Biomedical Imaging and director of Small Animal Imaging of Hollings Cancer Center. The brain tumor has a significant overall mortality, in part due to its location, difficulty of surgical treatment and the inability to get drugs through the blood-brain barrier, a protective barrier designed to keep a stable environment within and surrounding the brain.

In 40 percent of cases, standard treatments will extend life expectancy 4 to 7 months. “It’s really a dismal outcome. There are better ways to deliver standard of care.”

That’s where Broome and her nanotechnology lab enter in.

Nanotechnology is medicine, engineering, chemistry, and biology all bundled together and conducted at the nanoscale, between the range of 1 to 1,000 nanometers. For comparison, a thin newspaper page is about 100,000 nanometers thick. Broome and her team took what they know about the cancer’s biology and of platelet-derived growth factor (PDGF), one of numerous growth factor proteins that regulates cell growth and division and is also overexpressed on tumor cells in the brain. With that in mind, they engineered a micelle that is a phospholipid nanocarrier, “a bit of fat globule,” to deliver a concentrated dose of the chemotherapy drug temozolomide (TMZ) to the GBM tumor cells.

“Micelles of a certain size will cross the blood-brain barrier carrying a concentrated amount of TMZ,” she explained about how the nanotechnology works. “The PDGF is used much like a postal address. The micelle gets it to the street, and the PDGF gets it to the house.” This targeting ability is important because researchers have learned that it’s likely that the GBM will recur, she said.

“It’s thought that satellite cells left behind after surgical removal are the fastest growing and most dangerous ones. We’re trying to kill those rapidly growing satellite cells that will grow into new tumors in that location or others. These satellite tumors grow more aggressively than others. You have to hit them hard, fast and aggressively.”

Surprisingly, nanotechnology is already a part of everyday life in many ways that people don’t realize. It’s used in everything from makeup as moisturizers or UV sunscreens to ice cream to maintain frozen temperatures and creamy textures.

In medicine, Broome said, researchers construct nanocarriers that are stable and stealthy. “Your immune cells can’t attack them. They remain hidden.”When the package gets to where it’s going, nanotechnologists have various methods to get the micelles to release their payloads- one way is to use the acidic nature of a rapidly growing tumor. In normal circulation, the pH of blood is slightly alkaline and the micelle stays intact. What researchers have discovered is that in many tumor types, the pH drastically changes to an acidic environment.

“While the tumor is growing, it creates waste by-products and metabolites that alter the pH, thus lowering it. As the center becomes more necrotic, it becomes even more acidic.”

The change in pH triggers a release of the drug from our micelles just where clinicians want it to go to reduce toxicity to the rest of the body, she said.

“We take advantage of the tumor’s natural environment as well as the cellular expression. I’m a big proponent of understanding that microenvironment has an impact on how well you can treat tumors. It’s probably why so many therapeutics fail — because you have to take into account the immune system, the local environment, and the cells themselves — all three of these are important considerations.”

That’s why nanotechnology has an edge in shaping future cancer treatments.

“It’s very important that the public recognize that nanotechnology is the future. It impacts so many different fields. It has a clear impact on cancer biology and potentially has an impact on cancers that are inaccessible, untreatable, undruggable — that in normal circumstances are ultimately a death knell.”All too familiar with this is researcher and clinician Amy Lee Bredlau, M.D., director of MUSC Health’s Pediatric Brain Tumor Program, who also was a part of the study. Broome said she relishes having a clinician’s perspective in the lab to focus the group on translational outcomes for the patients.

“That’s why it’s so gratifying working with Amy Lee. She works with many cancers for which there are no options. We’re trying to provide options.”

Bredlau agreed. “This paper is exciting because it demonstrates a novel approach to treating brain tumors, combining nanotechnology targeting to a marker of brain tumors with a specialized delivery system. It will allow us eventually to target aggressive childhood and adult brain tumors.”

Bredlau said she’s taking time out from her clinical practice to be in Broome’s research lab because she knows that’s how she can best accelerate the process.

“I am passionate about improving the lives of my patients, now and in the future. Advancing research now is the best way to improve the lives of my patients to come.”

Bredlau sees nanotechnology as having the power to revolutionize treatment for brain tumors. “When we perfect this strategy, we will be able to deliver potent chemotherapies only to the area that needs them. This will dramatically improve our cure rates while cutting out a huge portion of our side effects from chemotherapy. Imagine a world where a cancer diagnosis not only was not life-threatening, but also did not mean that you would be tired, nauseated or lose your hair.”

Though excited by the study’s results, Broome cautions that there’s much more work to be done before new treatment options are readily available for patients.

“It may or may not be effective for all types of GBMs. There are subtypes as well as therapeutic-resistant GBMs that these nanocarriers may not impact. We need to continue rigorous testing to verify and validate our initial findings.”

They will be exploring an expanding field of targeted biomarkers available for GBM tumor cells. As is common in breast cancer and other cancer types, this cancer has specific cell surface receptors that are overexpressed, she said.

And though the drug TMZ in this protocol works very efficiently, it may not be the best drug for the majority of the people, she said. “Now that we know we can get the drug to its designated location and get it to work efficiently, we have a comparator. We can test more lethal and different combinations of drugs that have never before been used in this scenario.”

This method of drug delivery also opens new windows to immunotherapy treatments garnering recognition internationally. Broome wants to take chemotherapeutics and combine them with new immuno-therapeutic treatments to form unique combination delivery packages.

It’s ambitious.

Broome, whose team jokes that she keeps “a long, running list of impossible tasks,” said the work also translates to so many fields beyond cancer including stroke, transplant and regenerative medicine, where it could be used for example in wound healing in dermatology or organ maintenance in transplantation. It’s one reason she submitted her latest research to an international journal because she wants to accelerate advances in nanotechnology, a field she has no doubt will change how medicine is done.

“They are the primary reason I continue to do what I do,” she said of the patients who face grim diagnoses. “They give me hope. The possibilities for nanotherapeutics are endless and bright.”


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The above post is reprinted from materials provided by Medical University of South Carolina. The original item was written by Dawn Brazell. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kayla Miller, Suraj Dixit, Amy-Lee Bredlau, Alfred Moore, Emilie McKinnon, Ann-Marie Broome. Delivery of a drug cache to glioma cells overexpressing platelet-derived growth factor receptor using lipid nanocarriers.Nanomedicine, 2016; 11 (6): 581 DOI: 10.2217/nnm.15.218

Oak Ridge National Laboratory: Team Demonstrates large-scale technique to produce Quantum Dots


ORNL 051816 ornldemonstrUsing this 250-gallon reactor, ORNL researchers produced three-fourths of a pound of zinc sulfide quantum dots, shown in the inset. Credit: ORNL

A method to produce significant amounts of semiconducting nanoparticles for light-emitting displays, sensors, solar panels and biomedical applications has gained momentum with a demonstration by researchers at the Department of Energy’s Oak Ridge National Laboratory.

While nanoparticles – a type of quantum dot that is a semiconductor – have many potential applications, high cost and limited availability have been obstacles to their widespread use. That could change, however, because of a scalable ORNL technique outlined in a paper published in Applied Microbiology and Biotechnology.

Unlike conventional inorganic approaches that use expensive precursors, toxic chemicals, high temperatures and high pressures, a team led by ORNL’s Ji-Won Moon used bacteria fed by inexpensive sugar at a temperature of 150 degrees Fahrenheit in 25- and 250-gallon reactors. Ultimately, the team produced about three-fourths of a pound of zinc sulfide nanoparticles – without process optimization, leaving room for even higher yields.

The ORNL biomanufacturing technique is based on a platform technology that can also produce nanometer-size semiconducting materials as well as magnetic, photovoltaic, catalytic and phosphor materials. Unlike most biological synthesis technologies that occur inside the cell, ORNL’s biomanufactured quantum dot synthesis occurs outside of the cells. As a result, the nanomaterials are produced as loose particles that are easy to separate through simple washing and centrifuging.

 

The results are encouraging, according to Moon, who also noted that the ORNL approach reduces production costs by approximately 90 percent compared to other methods.

“Since biomanufacturing can control the quantum dot diameter, it is possible to produce a wide range of specifically tuned semiconducting nanomaterials, making them attractive for a variety of applications that include electronics, displays, solar cells, computer memory, energy storage, printed electronics and bio-imaging,” Moon said.

Successful biomanufacturing of light-emitting or semiconducting nanoparticles requires the ability to control material synthesis at the nanometer scale with sufficiently high reliability, reproducibility and yield to be cost effective. With the ORNL approach, Moon said that goal has been achieved.

Researchers envision their quantum dots being used initially in buffer layers of photovoltaic cells and other thin film-based devices that can benefit from their electro-optical properties as light-emitting materials.

Co-authors of the paper, titled “Manufacturing demonstration of microbially mediated zinc sulfide in pilot-plant scale reactors,” were ORNL’s Tommy Phelps, Curtis Fitzgerald Jr., Randall Lind, James Elkins, Gyoung Gug Jang, Pooran Joshi, Michelle Kidder, Beth Armstrong, Thomas Watkins, Ilia Ivanov and David Graham. Funding for this research was provided by DOE’s Advanced Manufacturing Office and Office of Science.

Explore further: Bacterial method for low-cost, environmentally-friendly synthesis of aqueous soluble quantum dot nanocrystals

More information: Ji-Won Moon et al. Manufacturing demonstration of microbially mediated zinc sulfide nanoparticles in pilot-plant scale reactors, Applied Microbiology and Biotechnology (2016). DOI: 10.1007/s00253-016-7556-y