University of Cambridge: Researchers to target hard-to-treat cancers


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A £10 million interdisciplinary collaboration is to target the most challenging of cancers using nanomedicine.

“We are going to pierce through the body’s natural barriers and deliver anti-cancer drugs to the heart of the tumour.” – George Malliaras

While the survival rate for most cancers has doubled over the past 40 years, some cancers such as those of the pancreas, brain, lung and oesophagus still have low survival rates.

Such cancers are now the target of an Interdisciplinary Research Collaboration (IRC) led by the University of Cambridge and involving researchers from Imperial College London, University College London and the Universities of Glasgow and Birmingham.

“Some cancers are difficult to remove by surgery and highly invasive, and they are also hard to treat because drugs often cannot reach them at high enough concentration,” explains George Malliaras, Prince Philip Professor of Technology in Cambridge’s Department of Engineering, who leads the IRC. “Pancreatic tumour cells, for instance, are protected by dense stromal tissue, and tumours of the central nervous system by the blood-brain barrier.”

The aim of the project, which is funded for six years by the Engineering and Physical Sciences Research Council, is to develop an array of new delivery technologies that can deliver almost any drug to any tumour in a large enough concentration to kill the cancerous cells.

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Chemists, engineers, material scientists and pharmacologists will focus on developing particles, injectable gels and implantable devices to deliver the drugs. Cancer scientists and clinicians from the Cancer Research UK Cambridge Centre and partner sites will devise and carry out clinical trials. Experts in innovative manufacturing technologies will ensure the devices are able to be manufactured and robust enough to withstand surgical manipulation.

One technology the team will examine is the ability of advanced materials to self-assemble and entrap drugs inside metal-organic frameworks. These structures can carry enormous amounts of drugs, and be tuned both to target the tumour and to release the drug at an optimal rate.

“We are going to pierce through the body’s natural barriers,” says Malliaras, “and deliver anti-cancer drugs to the heart of the tumour.”

Dr Su Metcalfe, a member of George Malliaras’s team and who is already using NanoBioMed to treat Multuple Sclerosis, added “the power of nanotechnology to synergise with potent anti-cancer drugs will be profound and the award will speed delivery to patients.”

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How nanotechnology is advancing drug delivery


Nanotechnology brings a lot to the medical field, and a specific branch known as nanomedicine has evolved because of the growing interest in this area.

Drug delivery systems derived from materials (or particles) at the nano-level provide a way for drugs, that might otherwise be toxic to the body, to reach their intended target through encapsulation or conjugation approaches.

There are some issues which need to be ironed out, with respect to the size of some of these carriers against the regulatory definitions, but it is an area that is expanding drug delivery approaches beyond what was previously possible with conventional approaches.

Inorganic Nanocarriers

Inorganic nanocarriers were the first type of nanotechnology-based drug delivery system to be trialled, yet their use and research is becoming less and less frequent. Many types of inorganic nanoparticle have been tried and tested, from gold, to iron oxide, to calcium phosphate, and beyond. Many inorganic nanoparticles are not biocompatible within the body, however, this can be overcome by functionalising the surface with organic molecules, such as PEG, to increase their compatibility within the body.

However, where this area has been let down is in their inability to be easily broken down after use and the subsequent difficulty to be excreted.

Organic Nanocarriers

Organic-based nanocarriers are the fastest growing area of nano-inspired drug delivery systems, and the reason for this expansion is due to the (often) inability of inorganic drug carriers to be broken down within the body and excreted. By comparison, the organic make-up of organic carriers, such as those made of certain types of polymers, dendrimer architectures and lipid-based encapsulating vessels (liposomes), can be broken down and excreted and offer a much greater degree of biocompatibility.

Each mechanism of delivery is different for these systems. For example, dendrimer-based delivery vessels will often have the drug covalently linked (conjugated) to the dendrimer backbone itself, and when it reaches a target of interest, certain functional groups at the edges will bind to the target and release the drug through molecular cleavage.

However, the most common way of delivering drugs is through encapsulation, as the toxicity (and the possibility of the drug interacting with the body before it reaches the target) is significantly reduced.

By using this approach, the nanocarrier can uptake the drug of interest into its core, where it is only released once the nanocarrier has reached the target of interest—thus lowering the risk of the drug being cleaved and released on route to the target site.

Solid Drug Nanoparticles

 Solid drug nanoparticles are another growing nanotechnology-inspired drug delivery system, but their use is not (yet) as widespread as organic delivery vessels. However, they do avoid some of the regulatory complications, as their use does not involve any extra species other than already approved drugs in an efficient nanoparticle form.

Solid drug nanoparticles are the nanoparticle form of a conventional drug; and take the form of being packed into a template, or as a suspension—therefore no delivery system is required and are administered by injection. The drug nanoparticles are often created through a bottom-up controlled precipitation of the drug to be administered, or by a top-down grinding approach of larger pieces of the drug until they are in the nanoparticle size range.

Aside from providing a more straightforward route to the clinic from a regulatory perspective, they also offer a way to tackle drug adherence issues—i.e. where people don’t take their required medication on time, which causes the effectiveness of the drug to be reduced—by providing a long-lasting, slow release of the drug over a period of 1 to 6 months.

Contributed and Written by Liam Critchley

Nano Magazine the magazine for Small Science

The $80 Trillion World Economy in One Chart: The World Bank View


The latest estimate from the World Bank puts global GDP at roughly $80 trillion in nominal terms for 2017.

Today’s chart from HowMuch.net uses this data to show all major economies in a visualization called a Voronoi diagram – let’s dive into the stats to learn more.

THE WORLD’S TOP 10 ECONOMIES

Here are the world’s top 10 economies, which together combine for a whopping two-thirds of global GDP.

Rank Country GDP % of Global GDP
#1 United States $19.4 trillion 24.4%
#2 China $12.2 trillion 15.4%
#3 Japan $4.87 trillion 6.1%
#4 Germany $3.68 trillion 4.6%
#5 United Kingdom $2.62 trillion 3.3%
#6 India $2.60 trillion 3.3%
#7 France $2.58 trillion 3.3%
#8 Brazil $2.06 trillion 2.6%
#9 Italy $1.93 trillion 2.4%
#10 Canada $1.65 trillion 2.1%

In nominal terms, the U.S. still has the largest GDP at $19.4 trillion, making up 24.4% of the world economy.

While China’s economy is far behind in nominal terms at $12.2 trillion, you may recall that the Chinese economy has been the world’s largest when adjusted for purchasing power parity (PPP) since 2016. 

The next two largest economies are Japan ($4.9 trillion) and Germany ($4.6 trillion) – and when added to the U.S. and China, the top four economies combined account for over 50% of the world economy.

MOVERS AND SHAKERS

Over recent years, the list of top economies hasn’t changed much – and in a similar visualization we posted 18 months ago, the four aforementioned top economies all fell in the exact same order.

However, look outside of these incumbents, and you’ll see that the major forces shaping the future of the global economy are in full swing, especially when it comes to emerging markets.

Here are some of the most important movements:

India has now passed France in nominal terms with a $2.6 trillion economy, which is about 3.3% of the global total. In the most recent quarter, Indian GDP growth saw its highest growth rate in two years at about 8.2%.

Brazil, despite its very recent economic woes, surpassed Italy in GDP rankings to take the #8 spot overall. 

Turkey has surpassed The Netherlands to become the world’s 17th largest economy, and Saudi Arabia has jumped past Switzerland to claim the 19th spot.

And what about the Future?

Read About How China will lead the world by 2050 Photo: REUTERS/Stringer

Read Genesis Nanotech News Online: Our Latest Edition


Genesis Nanotech News Online: Our Latest Edition with Articles Like –

Australian researchers design a rapid nano-filter that cleans dirty water 100X faster than current technology

Zombie Brain Cells Found in Mice

Energy Storage Technologies vie for Investmemt and Market Share

… AND …

Breakthrough Discovery: How groups of cells are able to build our tissues and organs while we are still embryos +

… 15 More Contributing Authors & Articles

Read Genesis Nanotech Online Here

#greatthingsfromsmallthings

Discovery: How groups of cells are able to build our tissues and organs while we are still embryos – Understanding ‘how’ may help us treat Cancer more effectively


 

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Ever wondered how groups of cells managed to build your tissues and organs while you were just an embryo?

Using state-of-the-art techniques he developed, UC Santa Barbara researcher Otger Campàs and his group have cracked this longstanding mystery, revealing the astonishing inner-workings of how embryos are physically constructed.

Not only does it bring a century-old hypothesis into the modern age, the study and its techniques provide the researchers a foundation to study other questions key to human health, such as how cancers form and spread or how to engineer organs.

“In a nutshell, we discovered a fundamental physical mechanism that cells use to mold embryonic tissues into their functional 3D shapes,” said Campàs, a professor of mechanical engineering in UCSB’s College of Engineering who holds the Duncan & Suzanne Mellichamp Chair in Systems Biology. His group investigates how living systems self organize to build the remarkable structures and shapes found in nature.

cell biology UC Santa B download

Cells coordinate by exchanging biochemical signals, but they also hold to and push on each other to build the body structures we need to live, such as the eyes, lungs and heart. And, as it turns out, sculpting the embryo is not far from glass molding or 3D printing. In their new work,”A fluid-to-solid jamming transition underlies vertebrate body axis elongation,” published in the journal Nature, Campàs and colleagues reveal that cell collectives switch from fluid to solid states in a controlled manner to build the vertebrate embryo, in a way similar to how we mold glass into vases or 3D print our favorite items. Or, if you like, we 3D print ourselves, from the inside.

Most objects begin as fluids. From metallic structures to gelatin desserts, their shape is made by pouring the molten original materials into molds, then cooling them to get the solid objects we use.

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A fluid-to-solid jamming transition underlies vertebrate body axis elongation

As in a Chihuly glass sculpture, made by carefully melting portions of glass to slowly reshape it into life, cells in certain regions of the embryo are more active and ‘melt’ the tissue into a fluid state that can be restructured. Once done, cells ‘cool down’ to settle the tissue shape, Campàs explained.

“The transition from fluid to solid tissue states that we observed is known in physics as ‘jamming’,” Campàs said. “Jamming transitions are a very general phenomena that happens when particles in disordered systems, such as foams, emulsions or glasses, are forced together or cooled down.”

This discovery was enabled by techniques previously developed by Campàs and his group to measure the forces between cells inside embryos, and also to exert miniscule forces on the cells as they build tissues and organs. Using zebrafish embryos, favored for their optical transparency but developing much like their human counterparts, the researchers placed tiny droplets of a specially engineered ferromagnetic fluid between the cells of the growing tissue.

The spherical droplets deform as the cells around them push and pull, allowing researchers to see the forces that cells apply on each other. And, by making these droplets magnetic, they also could exert tiny stresses on surrounding cells to see how the tissue would respond.

“We were able to measure physical quantities that couldn’t be measured before, due to the challenge of inserting miniaturized probes in tiny developing embryos,” said postdoctoral fellow Alessandro Mongera, who is the lead author of the paper.

“Zebrafish, like other vertebrates, start off from a largely shapeless bunch of cells and need to transform the body into an elongated shape, with the head at one end and tail at the other,” Campàs said.

UC Santa B II Lemaire

The physical reorganization of the cells behind this process had always been something of a mystery. Surprisingly, researchers found that the cell collectives making the tissue were physically like a foam (yes, as in beer froth) that jammed during development to ‘freeze’ the tissue architecture and set its shape.

These observations confirm a remarkable intuition made by Victorian-era Scottish mathematician D’Arcy Thompson 100 years ago in his seminal work “On Growth and Form.”

Darcy Thompson Ms48534_13Read About: D’Arcy Wentworth Thompson

“He was convinced that some of the physical mechanisms that give shapes to inert materials were also at play to shape living organisms. Remarkably, he compared groups of cells to foams and even the shaping of cells and tissues to glassblowing,” Campàs said. A century ago, there were no instruments that could directly test the ideas Thompson proposed, Campàs added, though Thompson’s work continues to be cited to this day.

The new Nature paper also provides a jumping-off point from which the Campàs Group researchers can begin to address other processes of embryonic development and related fields, such as how tumors physically invade surrounding tissues and how to engineer organs with specific 3D shapes.

“One of the hallmarks of cancer is the transition between two different tissue architectures. This transition can in principle be explained as an anomalous switch from a solid-like to a fluid-like tissue state,” Mongera explained. “The present study can help elucidate the mechanisms underlying this switch and highlight some of the potential druggable targets to hinder it.”

Alessandro Mongera, Payam Rowghanian, Hannah J. Gustafson, Elijah Shelton, David A. Kealhofer, Emmet K. Carn, Friedhelm Serwane, Adam A. Lucio, James Giammona & Otger Campàs

Nature (2018)

DOI: 10.1038%2Fs41586-018-0479-2

A Look at Graphene-Polymer Composite Medical Implants


This article is based around a talk given by Professor Alexander Seifalian from NanoRegMed Ltd, UK, at the NANOMED conference hosted by the NANOSMAT Society in Manchester on the 26-28th June 2018. In his talk, Alexander talks about how his company is developing a series of medical implants that are made from a biocompatible graphene-polymer composite.

Written and Contributed by: Liam Critchley

Link to Original AZ Nano Article

Regenerative medicine and tissue engineering have been around for a while now, but these fields continue to advance and are now utilizing many different types of nanomaterials. Alexander has created a wide range of prostheses, including a trachea, grafts for heart bypasses, tear ducts, ears, and noses using various materials; including graphene. There has been a need for many years to create grafts which have smaller diameters, are less prone to blockages and can be used in a human patient without it being rejected by the body.

Life Science / Shutterstock

Most of the biomaterials used in various prostheses have been around for many decades and still encounter problems. So, Alexander and his company have come up with a new range of materials involving graphene for these prosthesis applications.

There are not many areas of medical research where graphene is used, because graphene by itself can be toxic to humans if internalized. But this can be avoided by compositing graphene with other materials. Aside from its strength, graphene’s lightweight nature, antimicrobial properties, flexibility and corrosion resistance make it an ideal material for medical implants when it is formulated into biocompatible materials.

The materials developed by Alexander are a composite of polycaprolactone (PCL), and graphene and the materials can be tuned to be either biodegradable or non-biodegradable depending on the intended application. To make the material, they graft the graphene and then conjugate it to the polymers so that it sits within the polymer matrix, thus preventing it from being harmful to a patient. A critical aspect of why the materials work is because they integrate with the surrounding tissue and cells.

The fabricated materials are very strong, and it requires 80 kilos of force to break the composite. This high strength property can also be further improved, but it is at the expense of the viscoelasticity of the material, which is required for many implant applications. It is also possible to create polycarbonate-graphene composites using this method, but a higher concentration of graphene is required, and this again affects the viscoelastic properties of the composite. It is also possible to 3D print these composite materials into variously shaped scaffolds loaded with stem cells.

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Alexander has created many grafts with these materials, and they have been tested on mouse models. These grafts have been shown to grow cells, and the proliferated cells directly integrate with the tissue of interest to help with the growth of new tissue. This type of graft can also be loaded with nitrous oxide (sometimes alongside other kinds of particles or biological matter) and has excellent potential for wound healing applications.

Billion Photos / Shutterstock

Alexander has also created artificial arteries using these polymer-graphene composites. It was also possible to conjugated antibodies (made from peptides) inside the artery, which also becomes endothelialized under shear flow. The tunable nature of the composites has enabled Alexander to fabricate these pseudo-arteries with the same viscoelastic properties as natural arteries.

Because medical devices can take a while to become commercialized, all the products created from these composites are not at the commercial level just yet. However, they show a lot of promise and many have gone to clinical trials, with success. One of the key aspects that make this composite an exciting material is its tunability. The ratios can be altered such that it is flexible enough to be used as an artery, or it can be made more rigid for external prostheses, such as the nose. This, coupled with the fact that the materials are biocompatible, make it an interesting area to keep an eye on in the near future.

Sources:

• NANOMED 2018: http://www.nanomed.uk.com/

• NanoRegMed: http://www.nanoregmed.com/

Using PEG Nanotubes as Drug Delivery Systems


This article is based around a talk given by Ben Newland from Cardiff University, UK, at the NANOMED conference hosted by the NANOSMAT Society in Manchester on the 26-28th June 2018. In his talk, Ben talks about how he uses soft and flexible poly(ethylene glycol) (PEG) nanotubes to provide a sustained and localized delivery of therapeutic drugs.

Link to Original AZ Nano Article

Dr. Newland, a lecturer at Cardiff University, has been dealing with PEG nanotubes for approximately ten years after they came about as a side project to his other research. It should be noted that these nanotubes are not like carbon nanotubes, in that they are not electronically confined in 2 dimensions (i.e., a 1D material), nor are they carbon nanotubes functionalized with PEG at the surface. They are strictly hollow cylinders that are made entirely of PEG, and only bear the name nanotube because that is what they most closely resemble (without the capped end).

The research came about after previously working on carbon nanopipes, where a porous template was used to create hollow carbon nanostructures; in conjunction with another area of Ben’s research, which looks at using cyclized knotted polymers as drug delivery agents. To combine these areas, Ben poured a polymer solution (with a photo-initiator) into a porous template and shone UV light on it, which in turn cross-linked the polymers and created tube-like structures. This was the starting point of this research.

Since starting the research, Ben has incrementally polished the process and now produces polymer nanotubes which are 200 nm in diameter and up to 60 micrometers in length. Cyclized knot polymers are required to construct these nanotubes and can be made with commercially available PEG materials that contain di-vinyl groups. Different polymers have been trialed, and the PEG nanotubes were found to be the softest.

The possibility of using these for drug delivery applications came about after they were found to uptake rhodamine (a tracer dye). On the process side, Ben’s research team discovered that when the templates are dissolved (with sodium hydroxide) to leave just the nanotubes, the process breaks some of the ester bonds and creates an abundance of negative charges on the surface of the nanotubes.

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The anti-cancer drug, doxorubicin, was also found to be actively uptaken out of solution by the negatively charged nanotubes, and it is a straightforward procedure to determine the uptake and release of doxorubicin as it is intrinsically fluorescent and has a colored appearance. Ben’s work has led him to look at the release of doxorubicin from the nanotubes and found that they release most of the drug payload within the first five days, but there is a sustained delivery of 2-3 micrograms over 35 to 40 days. Some of the doxorubicin was found to stay in the nanotube, so while it is not perfect at the moment regarding the release, these nanotubes do show a lot of promise as new material as drug delivery agents.

One aspect of any delivery agent is that it needs to be biocompatible and low in cytotoxicity. In-vitro cell viability tests have been performed for these nanotubes at varying concentrations, and up to the point where the nanotubes are completely covering the cell. The results showed that even at the end (fully covered cells) the nanotubes did not kill the cell. Other cell viability studies on drug-loaded nanotubes found that the release of the drugs was killing the cells, and thus confirmed its position as a potential drug delivery agent.

The research has been taken further and has been tested on metastatic breast cancer cells in mice in conjunction with researchers from the University of Strathclyde. These studies have shown that the doxorubicin-loaded nanotubes reduced the tumor growth and reduced metastasis (the creation of secondary tumors away from the primary tumor site) in the mice.

Future studies will look at the cytotoxicity of the polymer nanotubes in-vivo and will look at how the drug release profile can be improved. Other areas will look at varying the size of the nanotubes, changing the chain length to alter the stiffness and entanglement of the nanotubes and looking at the effects of functionalizing the nanotubes with different nanoparticles.

Sources:

• NANOMED 2018: http://www.nanomed.uk.com/

• Ben Newland: http://www.newlandresearch.net/

Exploring Nanotechnology to Enhance Treatment, Diagnosis & Drug Discovery


What can you do with a liberal arts degree? Native New Yorker Daniel Heller, PhD, majored in history, added in some basic science courses, and started his working life as a middle school science teacher. After taking some additional chemistry coursework during non-teaching hours, Heller parlayed it all into a doctorate in chemistry from the University of Illinois.

Today he is a biomedical engineer at Memorial Sloan Kettering Cancer Center (MSKCC), New York City, where his Cancer Nanomedicine Laboratory team invents new technologies that can assist health care in helping human kind.

Heller chuckled when mentioning his circuitous life path and some of the stops along the way: performing as a wizard at a Renaissance Fair (“…liquid nitrogen turns into a pretty impressive potion…”), trying to master the Argentine tango, appreciating his brother’s equally non-traditional path as a drummer in heavy metal bands, and happily settling into married life with his wife who is a primary care physician.

In recent years, he has also managed to garner solid industry credentials in the form of awards, including the NSF CAREER Award (2018), Pershing Square Sohn Prize for Young Innovators in Cancer Research (2017), and NIH Director’s New Innovator Award (2012), among others.

“I like inventing,” Heller stated simply. “In my lab, we often think of ourselves as biomedical engineers whose primary goal is invent new technologies to improve cancer research, diagnosis, and therapy.

Only when I arrived at MSKCC did I realize how far that is from the way biologists think. I was trained that our goal is to invent, and to learn new science along the way, while a biologist’s goal is to understand nature and develop tools mainly as a means to an end. I didn’t have a huge biomedical background coming in, but by talking to the people around me at Sloan Kettering and Weill Cornell Medicine [where he is an Assistant Professor], I have learned a great deal.”

As detailed on his laboratory website (www.mskcc.org/research-areas/labs/daniel-heller), Heller and team are “… developing nanomedicines to target precision agents to disease sites, including to metastatic cancers. We are also addressing the problem of the early detection of cancer and other diseases by building implantable nanosensors.

To enable the discovery of new medicines, we also are inventing new nanosensors and imaging tools to accelerate drug development and biomedical research.”

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Nanoparticles in Treatment

Heller told Oncology Times that it all begins with interaction and collaboration. “We are lucky because we get to dig deep with the clinicians, clinician/scientists, and biologists to understand exactly what might be wrong with a particular mode of therapy,” said Heller of his development process. “An oncologist might talk to us about a drug or class of therapies that have particular problems and specific side effects, such as dose-limiting toxicity that prevents people from getting enough of a therapy to adequately inhibit the target in the tumor.”

He added that problems often stem from the fact that a drug negatively affects tissue that is not part of the tumor. “Can we avoid that one vulnerable tissue that will really mess up the use of this drug for treating the tumor? Can we prevent the drug from getting into that tissue?” asked Heller rhetorically. Clearly, he believes it is possible with the help of nanoparticles.

He noted that people erroneously think of nanoparticles as being “the smallest of the small.” But small molecule drugs, and even protein drugs, are much smaller than nanoparticles. Most drugs can diffuse all over the body. “But if we put the drug into a larger nanoparticle, we can keep it from spraying out over all the tissues,” detailed Heller.

His team also must consider how to deliver the nanoparticle containing the drug to a precise location in the tumor site, and whether there is a target that can lead it to that tumor site. “Most of the targets we are looking for are not on the tumor cells themselves, but on the blood vessels that are feeding the tumor,” said Heller. “Our targets are not drug targets, but rather gateways to the tumor, molecules on blood vessels in tumors sites, or sites of inflammation. Then we make sure that the nanoparticle has a molecule on the outside of it that can stick to those targets.”

The research takes the engineering team into the realms of vascular biology, vascular transport, and an understanding of how materials can get across the blood, across the blood/brain barrier, across the tumor barrier. “We are also exploring signaling pathways,” said Heller. “When trying to deliver a kinase inhibitor, for example, we must consider the target we are hitting, where else that target is in the body, and if there any other off-target proteins elsewhere in the body that the drug will hit. We also have to think about resistance mechanisms and compensatory pathways. So as a team we have been learning a lot of physiology.”

Heller says his 5-year-old laboratory contains requisite benches, a tissue culture room, and a studio equipped with lasers and optics for work on sensors. In the basement reside the all-important mice, critical to preclinical development and testing. Looking at target proteins in the body of a mouse, the team is able to determine if a drug encased in a nanoparticle hits the target, if it works better in a nanoparticle, and if it has the same side effects.

The eventual goal is to translate this understanding and these emerging technologies to clinical use and human patients. But it is a long row to hoe. “Once a technology is developed, it must go through the full ‘investigational new drug’ FDA process,” Heller lamented. “Even if a known compound is inside the particle, the whole particle is treated as a new drug.

That means we can’t just give it to clinicians to trial in patients; first the FDA must allow us to start a clinical trial.” Though regulatory delays are a frustration, the researcher said enthusiasm remains high because the potential of the new technologies is so powerful.

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Nanoparticles in Detection

The Cancer Nanomedicine Laboratory also maintains an interest in developing innovative approaches to cancer detection that is “… easier and more predictive. We found that we can detect some cancers earlier by measuring certain biomarkers in a person without having to take blood or biofluids to do it,” said Heller.

Instead, a tiny sensor made of carbon nanotubes is inserted inside a person. The nanotubes give off infrared light that can pass through tissues. “We can implant nanomaterial in a body, shoot light into it from outside the body, and then get a reading externally,” detailed Heller. “These nanomaterials are very sensitive to certain stimuli. We can put an antibody onto the surface of the nanotube and when it binds to an antigen we can see a signal change—a shift in the wavelength of the nanotube fluorescence—through the tissue.” (The team successfully detected ovarian cancer signaling changes in a mouse model. This work was detailed in a paper, Non-Invasive Ovarian Cancer Biomarker Detection via an Optical Nanosensor Implant, coauthored by Heller in Science Advances [2018;4(4):eaaq1090]).

Implications for future use of this technology in humans are significant. Heller said the first possible application could be in people with risk factors for certain diseases. “We could implant a biomarker or panel of biomarkers in people to detect early stage cancer, to measure cancer recurrence, or to monitor treatment and have earlier warning when therapy stops working.”

Asked how early the signaling changes would become apparent, Heller said it depends on the level of a given marker in the tissue. “With ovarian cancer, we would look at the technology as an intrauterine device, placed near the source of the cancer. If we were to wait for biomarkers to reach a high enough level to be detected in the blood, we likely would be dealing with late-stage cancer. If we can measure that biomarker right next to the ovaries or fallopian tube, we would see signal changes at an even earlier point in the life cycle of the cancer.”

Looking downstream of this work, Heller said the team is already questioning if it might be possible to insert a small sensor under the skin, in the blood, or even in a tattoo to measure all kinds of biomarkers, then report a whole panel in real time, at early stages, back to a wearable Fitbit-like device. “The long-term hope is to find super easy ways to measure lots of biomarkers in real time,” said Heller.

Back to Top | Article Outline

Nanoparticles in Discovery

A third aspect of the work underway in Heller’s lab focuses on making research tools, specifically using carbon nanotubes as sensors in drug discovery assays. Heller believes the sensors will be able to measure things that have not been measurable before, or measured in ways that could not be accomplished before, such as in living cells and living tissue. “By measuring an analyte inside living cells or living tissue in mice, we gain the ability to do studies that cannot be done otherwise. This will allow us to address new hypotheses, and it will be helpful for drug development and for basic researchers at institutions such as MSKCC.”

Heller stressed that it is exactly institutions like MSKCC that can lead the way in helping biomedical engineers interact more fully with biomedical researchers. “Even though both of these concepts have the word ‘biomedical’ in them, ‘biomedical engineering’ departments come from engineering schools, while ‘biomedical research’ comes from places that often do not have engineering schools.

So there is a disconnect,” said Heller. “I realize how valuable it is to me as an engineering researcher to be in a biomedical institution and come in contact with the people who study biomedical questions and understand the medical problems. Biomedical institutions would benefit greatly from organized efforts to bring in engineering researchers whose goal it is to understand and make new technologies to address their problems.”

Heller laughed at the suggestion that some of the things he makes sound like cinematic props from the vintage sci-fi flick, The Incredible Voyage. “Sometimes people think we are the science fiction lab of Memorial Sloan Kettering,” he admitted with humor. And when asked if the younger history student/middle school teacher/or physical scientist in him ever thinks, “I can’t believe I am doing this kind of stuff,” he answered without hesitation, “Yeah, all the time. I think I have gotten to where I am by not defining myself. It’s important to be flexible. Where does it stop? It doesn’t. If you keep changing you can aspire to do anything you want.”

Valerie Neff Newitt is a contributing writer.

Quantum dots could aid in fight against Parkinson’s


A large team of researchers with members from several institutions in the U.S., Korea and Japan has found that injecting quantum dots into the bloodstreams of mice led to a reduction in fibrils associated with Parkinson’s disease. In their paper published in the journal Nature Nanotechnology, the group describes their studies of the impact of quantum dots made of graphene on synuclein and what they found.

Quantum dots are particles that exist at the nanoscale and are made of semiconducting materials. Because they exhibit quantum properties, scientists have been conducting experiments to learn more about changes they cause to organisms when embedded in their cells. In this new effort, the researchers became interested in the idea of embedding quantum dots in synuclein cells.

Synucleins make up a group or family of proteins and are typically found in neural tissue.

One type, an alpha-synuclein, has been found to be associated with the formation of fibrils as part of the development of Parkinson’s disease. To see how such a protein might react when exposed to quantum dots, the researchers combined the two in a petri dish and watched what happened. They found that the quantum dots became bound to the protein, and in so doing, prevented it from clumping into fibrils. They also found that doing so after fibrils had already formed caused them to come apart. Impressed with their findings, the team pushed their research further.

Noting that quantum dots are small enough to pass through the blood/brain barrier, they injected quantum dots into mice with induced Parkinson’s disease and monitored them for several months. They report that after six months, the mice showed improvements in symptoms.

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Quantum dots in brain could treat Parkinson’s and Alzheimer’s diseases

The researchers suggest that quantum dots might have a similar impact on multiple ailments where fibrilization occurs, noting that another team had found that injecting them into Alzheimer’s mouse models produced similar results.

It is still not known if injecting similar or different types of quantum dots into human patients might have the same effect, they note. Nor is it known if doing so would have any undesirable side effects. Still, the researchers are optimistic about the idea of using quantum dots for treatment of such diseases and because of that, have initiated plans for testing with other animals—and down the road they are looking at the possibility of conducting clinical trials in humans.

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Graphene smart contact lenses could give you thermal infrared and UV vision


A breakthrough in graphene imaging technology means you might soon have a smart contact lens, or other ultra-thin device, with a built-in camera that also gives you infrared “heat vision.” By sandwiching two layers of graphene together, engineers at the University of Michigan have created an ultra-broadband graphene imaging sensor that is ultra-broadband (it can capture everything from visible light all the way up to mid-infrared) — but more importantly, unlike other devices that can see far into the infrared spectrum, it operates well at room temperature.

As you probably know by now, graphene has some rather miraculous properties — including, as luck would have it, a very strong effect when it’s struck by photons (light energy). Basically, when graphene is struck by a photon, an electron absorbs that energy and becomes a hot carrier — an effect that can be measured, processed, and turned into an image. The problem, however, is that graphene is incredibly thin (just one atom thick) and transparent — and so it only absorbs around 2.3% of the light that hits it. With so little light striking it, there just aren’t enough hot carrier electrons to be reliably detected. (Yes, this is one of those rare cases where being transparent and super-thin is actually a bad thing.)

Zhaohui Zhong and friends at the University of Michigan, however, have devised a solution to this problem. They still use a single layer of graphene as the primary photodetector — but then they put an insulating dielectric beneath it, and then another layer of graphene beneath that. When light strikes the top layer, the hot carrier tunnels through the dielectric to the other side, creating a charge build-up and strong change in conductance. In effect, they have created a phototransistor that amplifies the small number of absorbed photons absorbed by the top layer (gate) into a large change in the bottom layer’s conductance (channel).

In numerical terms, raw graphene generally produces a few milliamps of power per watt of light energy (mA/W) —  the Michigan phototransistor, however, is around 1 A/W, or around 100 times more sensitive. This is around the same sensitivity as CMOS silicon imaging sensors in commercial digital cameras.

The prototype device created by Zhong and co. is already “smaller than a pinky nail” and can be easily scaled down. By far the most exciting aspect here is the ultra-broadband sensitivity — while the silicon sensor in your smartphone can only register visible light, graphene is sensitive to a much wider range of wavelengths, from ultraviolet at the bottom, all the way to far-infrared at the top.

In this case, the Michigan phototransistor is sensitive to visible light and up to mid-infrared — but it’s entirely possible that a future device would cover UV and far-IR as well.

There are imaging technologies that can see in the UV and IR ranges, but they generally require bulky cryogenic cooling equipment; the graphene phototransistor, on the other hand, is so sensitive that it works at room temperature. [Research paper: doi:10.1038/nnano.2014.31 – “Graphene photodetectors with ultra-broadband and high responsivity at room temperature”]

Now, I think we can all agree that a smartphone that can capture UV and IR would be pretty damn awesome — but because this is ultra-thin-and-light-and-efficient graphene we’re talking about, the potential, futuristic applications are far more exciting. For me, the most exciting possibility is building graphene imaging technology into smart contact lenses. At first, you might just use this data to take awesome photos of the environment, or to give you you night/thermal vision through a display built into the contact lens. In the future, though, as bionic eyes and retinal implants improve, we might use this graphene imaging tech to wire UV and IR vision directly into our brains.

Imagine if you could look up at the sky, and instead of seeing the normal handful of stars, you saw this:

The Milky Way, as seen by NASA’s infrared Spitzer telescope

That’d be pretty sweet.