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 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 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

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.


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.

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.


Nanorobots target cancerous tumours with precision

Nanorobots 081916 legionsofnanThe legions of nanorobotic agents are actually composed of more than 100 million flagellated bacteria — and therefore self-propelled — and loaded with drugs that moved by taking the most direct path between the drug’s injection point and …more

Researchers from Polytechnique Montréal, Université de Montréal and McGill University have just achieved a spectacular breakthrough in cancer research. They have developed new nanorobotic agents capable of navigating through the bloodstream to administer a drug with precision by specifically targeting the active cancerous cells of tumours. This way of injecting medication ensures the optimal targeting of a tumour and avoids jeopardizing the integrity of organs and surrounding healthy tissues. As a result, the drug dosage that is highly toxic for the human organism could be significantly reduced.

This scientific breakthrough has just been published in the prestigious journal Nature Nanotechnology in an article titled “Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.” The article notes the results of the research done on mice, which were successfully administered nanorobotic agents into colorectal tumours.

“These legions of nanorobotic agents were actually composed of more than 100 million flagellated bacteria – and therefore self-propelled – and loaded with drugs that moved by taking the most direct path between the drug’s injection point and the area of the body to cure,” explains Professor Sylvain Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory, who heads the research team’s work. “The drug’s propelling force was enough to travel efficiently and enter deep inside the tumours.”

When they enter a tumour, the nanorobotic agents can detect in a wholly autonomous fashion the oxygen-depleted tumour areas, known as hypoxic zones, and deliver the drug to them. This hypoxic zone is created by the substantial consumption of oxygen by rapidly proliferative tumour cells. Hypoxic zones are known to be resistant to most therapies, including radiotherapy.

But gaining access to tumours by taking paths as minute as a and crossing complex physiological micro-environments does not come without challenges. So Professor Martel and his team used nanotechnology to do it.

Bacteria with compass

To move around, bacteria used by Professor Martel’s team rely on two natural systems. A kind of compass created by the synthesis of a chain of magnetic nanoparticles allows them to move in the direction of a magnetic field, while a sensor measuring oxygen concentration enables them to reach and remain in the tumour’s active regions. By harnessing these two transportation systems and by exposing the bacteria to a computer-controlled magnetic field, researchers showed that these bacteria could perfectly replicate artificial nanorobots of the future designed for this kind of task.

“This innovative use of nanotransporters will have an impact not only on creating more advanced engineering concepts and original intervention methods, but it also throws the door wide open to the synthesis of new vehicles for therapeutic, imaging and diagnostic agents,” Professor Martel adds. “Chemotherapy, which is so toxic for the entire human body, could make use of these natural nanorobots to move drugs directly to the targeted area, eliminating the harmful side effects while also boosting its therapeutic effectiveness.”

Explore further: Fantastic voyage: From science fiction to reality

More information: Ouajdi Felfoul et al, Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions, Nature Nanotechnology (2016). DOI: 10.1038/NNANO.2016.137


Quantum dots with impermeable shell used as a powerful tool for “nano-engineering”

QDs Shell 081116 160811101152_1_540x360Images of ZnO quantum dots prepared by the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw, taken by transmission electron microscopy. False colors.
Credit: IPC PAS

Unique optical features of quantum dots make them an attractive tool for many applications, from cutting-edge displays to medical imaging. Physical, chemical or biological properties of quantum dots must, however, be adapted to the desired needs.

Unfortunately, up to now quantum dots prepared by chemical methods could only be functionalized using copper-based click reactions with retention of their luminescence. This obstacle can be ascribed to the fact that copper ions destroy the ability of quantum dots to emit light. Scientists from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw and the Faculty of Chemistry of the Warsaw University of Technology (FC WUT) have shown, however, that zinc oxide (ZnO) quantum dots prepared by an original method developed by them, after modification by the click reaction with the participation of copper ions, fully retain their ability to emit light.

“Click reactions catalyzed by copper cations have long attracted the attention of chemists dealing with quantum dots. The experimental results, however, were disappointing: after modification, the luminescence was so poor that they were just not fit for use. We were the first to demonstrate that it is possible to produce quantum dots from organometallic precursors in a way they do not lose their valuable optical properties after being subjected to copper-catalysed click reactions,” says Prof. Janusz Lewinski (IPC PAS, FC WUT).

Quantum dots are crystalline structures with size of a few nanometers (billionth parts of a meter). As semiconductor materials, they exhibit a variety of interesting features typical of quantum objects, including absorbing and emitting radiation of only a strictly defined energy. Since atoms interact with light in a similar way, quantum dots are often called artificial atoms. In some respects, however, quantum dots offer more possibilities than atoms. Optical properties of each dot actually depend on its size and the type of material from which it is formed. This means that quantum dots may be precisely designed for specific applications.

To meet the need of specific applications, quantum dots have to be tailored in terms of physico-chemical properties. For this purpose, chemical molecules with suitable characteristics are attached to their surface. Due to the simplicity, efficacy, and speed of the process, an exceptionally convenient method is the click reaction. Unfortunately, one of the most widely used click reactions takes place with the participation of copper ions, which was reported to result in the almost complete quenching of the luminescence of the quantum dots.

“Failure is usually a result of the inadequate quality of quantum dots, which is determined by the synthesis method. Currently, ZnO dots are mainly produced by the sol-gel method from inorganic precursors. Quantum dots generated in this manner are coated with a heterogeneous and probably leaky protective shell, made of various sorts of chemical molecules. During a click reaction, the copper ions are in direct contact with the surface of quantum dots and quench the luminescence of the dot, which becomes completely useless,” explains Dr. Agnieszka Grala (IPC PAS), the first author of the article in the Chemical Communications journal.

For several years, Prof. Lewinski’s team has been developing alternative methods for the preparation of high quality ZnO quantum dots. The method presented in this paper affords the quantum dots derived from organozinc precursors. Composition of the nanoparticles can be programmed at the stage of precursors preparation, which makes it possible to precisely control the character of their organic-inorganic interface.

“Nanoparticles produced by our method are crystalline and all have almost the same size. They are spherical and have characteristics of typical quantum dots. Every nanoparticle is stabilized by an impermeable protective jacket, built of organic compounds, strongly anchored on the surface of the semiconductor core. As a result, our quantum dots remain stable for a long time and do not aggregate, that is clump together, in solutions,” describes Malgorzata Wolska-Pietkiewicz, a PhD student at FC WUT.

“The key to success is producing a uniform stabilizing shell. Such coatings are characteristic of the ZnO quantum dots obtained by our method. The organic layer behaves as a tight protective umbrella protecting dots from direct influence of the copper ions,” says Dr. Grala and clarifies: “We carried out click reaction known as alkyne-azide cycloaddition, in which we used a copper(l) compound as catalysts. After functionalization, our quantum dots shone as brightly as at the beginning.”

Quantum dots keep finding more and more applications in various industrial processes and as nanomarkers in, among others, biology and medicine, where they are combined with biologically active molecules. Nanoobjects functionalized in this manner are used to label both individual cells as well as whole tissues. The unique properties of quantum dots also enable long-term monitoring of the labelled item. Commonly used quantum dots, however, contain toxic heavy metals, including cadmium. In addition, they clump together in solutions, which supports the thesis of the lack of tightness of their shells. Meanwhile, the ZnO dots produced by Prof. Lewinski’s group are non-toxic, they do not aggregate, and can be bound to many chemical compounds — so they are much more suitable for medical diagnosis and for imaging cells and tissues.

Research on the methods of production of functionalized ZnO quantum dots was carried out under an OPUS grant from the Poland’s National Science Centre.

Story Source:

The above post is reprinted from materials provided by Institute of Physical Chemistry of the Polish Academy of Sciences.Note: Content may be edited for style and length.

Journal Reference:

  1. Agnieszka Grala, Małgorzata Wolska-Pietkiewicz, Wojciech Danowski, Zbigniew Wróbel, Justyna Grzonka, Janusz Lewiński. ‘Clickable’ ZnO nanocrystals: the superiority of a novel organometallic approach over the inorganic sol–gel procedure. Chem. Commun., 2016; 52 (46): 7340 DOI:10.1039/C6CC01430E

University of Copenhagen: Nanoparticles Provide Gentle Cancer Treatment that Works!

Coppen Cancer 081116 160803103750_1_540x360The images show PET scans of a mouse with a large tumor (by the white arrow). The tumor is treated with nanoparticles, which are injected directly into the tumor and are then flashed with near infrared laser light. The laser light heats the nanoparticles, thus damaging or killing the cancer cells (red arrows).
Credit: Kamilla Nørregaard and Jesper Tranekjær Jørgensen, Panum Inst.

Cancer treatments based on laser irridation of tiny nanoparticles that are injected directly into the cancer tumor are working and can destroy the cancer from within. Researchers from the Niels Bohr Institute and the Faculty of Health Sciences at the University of Copenhagen have developed a method that kills cancer cells using nanoparticles and lasers. The treatment has been tested on mice and it has been demonstrated that the cancer tumors are considerably damaged. The results are published in the scientific journal,Scientific Reports.

Traditional cancer treatments like radiation and chemotherapy have major side affects, because they not only affect the cancer tumors, but also the healthy parts of the body. A large interdisciplinary research project between physicists at the Niels Bohr Institute and doctors and human biologists at the Panum Institute and Rigshospitalet has developed a new treatment that only affects cancer tumors locally and therefore is much more gentle on the body.

The project is called Laser Activated Nanoparticles for Tumor Elimination (LANTERN). The head of the project is Professor Lene Oddershede, a biophysicist and head of the research group Optical Tweezers at the Niels Bohr Institute at the University of Copenhagen in collaboration with Professor Andreas Kjær, head of the Cluster for Molecular Imaging, Panum Institute.

After experimenting with biological membranes, the researchers have now tested the method on living mice. In the experiments, the mice are given cancer tumors of laboratory cultured human cancer cells.

“The treatment involves injecting tiny nanoparticles directly into the cancer. Then you heat up the nanoparticles from outside using lasers. It is a strong interaction between the nanoparticles and the laser light, which causes the particles to heat up. What then happens is that the heated particles damage or kill the cancer cells,” explains Lene Oddershede.

Design and effect

The small nanoparticles are between 80 and 150 nanometers in diameter (a nanometer is a millionth of a millimeter). The tested particles consist of either solid gold or a shell structure consisting of a glass core with a thin shell of gold around it. Some of the experiments aimed to find out which particles are most effective in reducing tumors.

“As physicists we have great expertise in the interaction between light and nanoparticles and we can very accurately measure the temperature of the heated nanoparticles. The effectiveness depends on the right combination between the structure and material of the particles, their physical size and the wavelength of the light,” explains Lene Oddershede.

The experiments showed that the researchers got the best results with nanoparticles that were 150 nanometers in size and consisted of a core of glass coated with gold. The nanoparticles were illuminated with near-infrared laser light, which is the best at penetrating through the tissue. In contrast to conventional radiation therapy, the near-infrared laser light causes no burn damage to the tissue that it passes through. Just an hour after the treatment, they could already directly see with PET scans that the cancer cells had been killed and the effect continued for at least two days after the treatment.

“Now we have proven that the method works. In the longer term, we would like the method to work by injecting the nanoparticles into the bloodstream, where they end up in the tumors that may have metastasized. With the PET scans we can see where the tumors are and irridate them with lasers, while also effectively assessing how well the treatment has worked shortly after the irradiation. In addition, we will coat the particles with chemotherapy, which is released by the heat and which will also help kill the cancer cells,” explains Lene Oddershede.

Story Source:

The above post is reprinted from materials provided byUniversity of Copenhagen – Niels Bohr Institute. Note: Content may be edited for style and length.

Journal Reference:

  1. Jesper Tranekjær Jørgensen, Kamilla Norregaard, Pengfei Tian, Poul Martin Bendix, Andreas Kjaer, Lene B. Oddershede. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy. Scientific Reports, 2016; 6: 30076 DOI: 10.1038/srep30076