MIT: Nanoparticles take a “Fantastic, (magnetic) Voyage” – Helping Drug-Delivery Nanoparticles Reach Their Targets (with Video)


MIT-Magnetic-Micropropellers_0MIT engineers have designed a magnetic microrobot that can help push drug-delivery particles into tumor tissue (left). They also employed swarms of naturally magnetic bacteria to achieve the same effect (right). Image courtesy of the researchers.

Tiny robots powered by magnetic fields could help drug-delivery nanoparticles reach their targets.

MIT engineers have designed tiny robots that can help drug-delivery nanoparticles push their way out of the bloodstream and into a tumor or another disease site. Like crafts in “Fantastic Voyage” — a 1960s science fiction film in which a submarine crew shrinks in size and roams a body to repair damaged cells — the robots swim through the bloodstream, creating a current that drags nanoparticles along with them.

The magnetic microrobots, inspired by bacterial propulsion, could help to overcome one of the biggest obstacles to delivering drugs with nanoparticles: getting the particles to exit blood vessels and accumulate in the right place.

“When you put nanomaterials in the bloodstream and target them to diseased tissue, the biggest barrier to that kind of payload getting into the tissue is the lining of the blood vessel,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, and the senior author of the study.

“Our idea was to see if you can use magnetism to create fluid forces that push nanoparticles into the tissue,” adds Simone Schuerle, a former MIT postdoc and lead author of the paper, which appears in the April 26 issue of Science Advances.

In the same study, the researchers also showed that they could achieve a similar effect using swarms of living bacteria that are naturally magnetic. Each of these approaches could be suited for different types of drug delivery, the researchers say.

Tiny robots

Schuerle, who is now an assistant professor at the Swiss Federal Institute of Technology (ETH Zurich), first began working on tiny magnetic robots as a graduate student in Brad Nelson’s Multi-scale Robotics Lab at ETH Zurich. When she came to Bhatia’s lab as a postdoc in 2014, she began investigating whether this kind of bot could help to make nanoparticle drug delivery more efficient.

In most cases, researchers target their nanoparticles to disease sites that are surrounded by “leaky” blood vessels, such as tumors. This makes it easier for the particles to get into the tissue, but the delivery process is still not as effective as it needs to be.

The MIT team decided to explore whether the forces generated by magnetic robots might offer a better way to push the particles out of the bloodstream and into the target site.

The robots that Schuerle used in this study are 35 hundredths of a millimeter long, similar in size to a single cell, and can be controlled by applying an external magnetic field. This bio-inspired robot, which the researchers call an “artificial bacterial flagellum,” consists of a tiny helix that resembles the flagella that many bacteria use to propel themselves. These robots are 3-D-printed with a high-resolution 3-D printer and then coated with nickel, which makes them magnetic.

To test a single robot’s ability to control nearby nanoparticles, the researchers created a microfluidic system that mimics the blood vessels that surround tumors. The channel in their system, between 50 and 200 microns wide, is lined with a gel that has holes to simulate the broken blood vessels seen near tumors.

Using external magnets, the researchers applied magnetic fields to the robot, which makes the helix rotate and swim through the channel. Because fluid flows through the channel in the opposite direction, the robot remains stationary and creates a convection current, which pushes 200-nanometer polystyrene particles into the model tissue. These particles penetrated twice as far into the tissue as nanoparticles delivered without the aid of the magnetic robot.

This type of system could potentially be incorporated into stents, which are stationary and would be easy to target with an externally applied magnetic field. Such an approach could be useful for delivering drugs to help reduce inflammation at the site of the stent, Bhatia says.

Bacterial swarms

The researchers also developed a variant of this approach that relies on swarms of naturally magnetotactic bacteria instead of microrobots. Bhatia has previously developed bacteria that can be used to deliver cancer-fighting drugs and to diagnose cancer, exploiting bacteria’s natural tendency to accumulate at disease sites.

For this study, the researchers used a type of bacteria called Magnetospirillum magneticum, which naturally produces chains of iron oxide. These magnetic particles, known as magnetosomes, help bacteria orient themselves and find their preferred environments.

The researchers discovered that when they put these bacteria into the microfluidic system and applied rotating magnetic fields in certain orientations, the bacteria began to rotate in synchrony and move in the same direction, pulling along any nanoparticles that were nearby. In this case, the researchers found that nanoparticles were pushed into the model tissue three times faster than when the nanoparticles were delivered without any magnetic assistance.

This bacterial approach could be better suited for drug delivery in situations such as a tumor, where the swarm, controlled externally without the need for visual feedback, could generate fluidic forces in vessels throughout the tumor.

The particles that the researchers used in this study are big enough to carry large payloads, including the components required for the CRISPR genome-editing system, Bhatia says. She now plans to collaborate with Schuerle to further develop both of these magnetic approaches for testing in animal models.

The research was funded by the Swiss National Science Foundation, the Branco Weiss Fellowship, the National Institutes of Health, the National Science Foundation, and the Howard Hughes Medical Institute.

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Washington State U – Bio-inspired nanoscale Research – Nano-Flowers may lead lead to more effective drug delivery and diagnostics for cancer and other illnesses


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Schematic representation of the movement of the flower-like particle as it makes its way through a cellular trap to deliver therapeutic genes.
Credit: WSU

Washington State University researchers have developed a novel way to deliver drugs and therapies into cells at the nanoscale without causing toxic effects that have stymied other such efforts.

The work could someday lead to more effective therapies and diagnostics for cancer and other illnesses.

Led by Yuehe Lin, professor in WSU’s School of Mechanical and Materials Engineering, and Chunlong Chen, senior scientist at the Department of Energy’s Pacific Northwest National Laboratory (PNNL), the research team developed biologically inspired materials at the nanoscale that were able to effectively deliver model therapeutic genes into tumor cells. They published their results in the journal, Small.

Researchers have been working to develop nanomaterials that can effectively carry therapeutic genes directly into the cells for the treatment of diseases such as cancer. The key issues for gene delivery using nanomaterials are their low delivery efficiency of medicine and potential toxicity.

“To develop nanotechnology for medical purposes, the first thing to consider is toxicity — That is the first concern for doctors,” said Lin.

The flower-like particle the WSU and PNNL team developed is about 150 nanometers in size, or about one thousand times smaller than the width of a piece of paper. It is made of sheets of peptoids, which are similar to natural peptides that make up proteins. The peptoids make for a good drug delivery particle because they’re fairly easy to synthesize and, because they’re similar to natural biological materials, work well in biological systems.

The researchers added fluorescent probes in their peptoid nanoflowers, so they could trace them as they made their way through cells, and they added the element fluorine, which helped the nanoflowers more easily escape from tricky cellular traps that often impede drug delivery.

The flower-like particles loaded with therapeutic genes were able to make their way smoothly out of the predicted cellular trap, enter the heart of the cell, and release their drug there.

“The nanoflowers successfully and rapidly escaped (the cell trap) and exhibited minimal cytotoxicity,” said Lin.

After their initial testing with model drug molecules, the researchers hope to conduct further studies using real medicines.

“This paves a new way for us to develop nanocargoes that can efficiently deliver drug molecules into the cell and offers new opportunities for targeted gene therapies,” he said.

The WSU and PNNL team have filed a patent application for the new technology, and they are seeking industrial partners for further development.

Story Source:

Materials provided by Washington State UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Yang Song, Mingming Wang, Suiqiong Li, Haibao Jin, Xiaoli Cai, Dan Du, He Li, Chun-Long Chen, Yuehe Lin. Efficient Cytosolic Delivery Using Crystalline Nanoflowers Assembled from Fluorinated PeptoidsSmall, 2018; 14 (52): 1803544 DOI: 10.1002/smll.201803544

Healing Kidneys with Nanotechnology – ASU Researchers Explore a new horizon for DNA Nanotechnology


healingkidne (1)The illustration shows a diseased kidney on the left and a healthy kidney on the right, after rectangular DNA nanostructures migrated and accumulated in the kidney, acting to alleviate damage due to oxidative stress. Credit: Shireen Dooling

Each year, there are some 13.3 million new cases of acute kidney injury (AKI), a serious affliction. Formerly known as acute renal failure, the ailment produces a rapid buildup of nitrogenous wastes and decreases urine output, usually within hours or days of disease onset. Severe complications often ensue.

AKI is responsible for 1.7 million deaths annually. Protecting healthy kidneys from harm and treating those already injured remains a significant challenge for modern medicine.

In new research appearing in the journal Nature Biomedical Engineering, Hao Yan and his colleagues at the University of Wisconsin-Madison and in China describe a new method for treating and preventing AKI. Their technique involves the use of tiny, self-assembling forms measuring just billionths of a meter in diameter.

The triangular, tubular and rectangular shapes are designed and built using a method known as DNA origami. Here, the base pairing properties of DNA’s four nucleotides are used to engineer and fabricate DNA origami nanostructures (DONs), which self-assemble and preferentially accumulate in kidneys.

“The interdisciplinary collaboration between nanomedicine and the in-vivo imaging team led by professor Weibo Cai at the University of Wisconsin-Madison and the DNA nanotechnology team has led to a novel application—applying DNA origami nanostructures to treat ,” Yan says. “This represents a new horizon for DNA nanotechnology research.”

Experiments described in the new study—conducted in mice as well as human embryonic kidney cells—suggest that DONs act as a rapid and active kidney protectant and may also alleviate symptoms of AKI. The distribution of DONs was examined with positron emission tomography (PET). Results showed that the rectangular nanostructures were particularly successful, protecting the kidneys from harm as effectively as the leading drug therapy and alleviating a leading source of AKI known as .

The study is the first to explore the distribution of DNA nanostructures in a living system by means of quantitative imaging with PET and paves the way for a host of new therapeutic approaches for the treatment of AKI as well as other renal diseases.

“This is an excellent example of team science, with multidisciplinary and multinational collaboration,” Cai said. “The four research groups are located in different countries, but they communicate regularly and have synergistic expertise. The three equally-contributing first authors (Dawei Jiang, Zhilei Ge, Hyung-Jun Im) also have very different backgrounds, one in radiolabeling and imaging, one in DNA nanostructures, and the other in clinical nuclear medicine. Together, they drove the project forward.”

Vital organ

Kidneys perform essential roles in body, removing waste and extra water from the blood to form urine. Urine then flows from the kidneys to the bladder through the ureters. Wastes in the blood are produced from the normal breakdown of active muscle and from foods, which the body requires for energy and self-repair.

Acute kidney injury can range considerably in severity. In advanced AKI, kidney transplantation is required as well as supportive therapies including rehydration and dialysis. Contrast-induced AKI, a common form of the illness, is caused by contrast agents sometimes used to improve the clarity of medical imaging. An anti-oxidant drug known as N-acetylcysteine (NAC) is used clinically to protect the kidneys from toxic assault during such procedures, but poor bioavailability of the drug in the kidneys can limit its effectiveness. (Currently, there is no known cure for AKI.)

Nanomedicinethe engineering of atoms or molecules at the nanoscale for biomedical applications—represents a new and exciting avenue of medical exploration and therapy. Recent research in the field has driven advances leading to improved imaging and therapeutics for a range of diseases, including AKI, though the use of nanomaterials within living systems in order to treat  has thus far been limited.

Healing kidneys with nanotechnology
Hao Yan directs the Biodesign Center for Molecular Design and Biomimetics and is the Martin D. Glick Distinguished Professor in the School of Molecular Sciences at ASU. Credit: The Biodesign Institute at Arizona State University

The base-pairing properties of nucleic acids like DNA and RNA enable the design of tiny programmable structures of predictable shape and size, capable of performing a multitude of tasks. Further, these nanoarchitectures are desirable for use in living systems due to their stability, low toxicity, and low immunogenicity.

New designs

The current study marks the first investigation of DNA origami nanostructures within living organisms, using quantitative imaging to track their behavior. The PET imaging used in the study allowed for a quantitative and reliable real-time method to study the circulation of DONs in a living organism and to assess their physiological distribution. Rectangular DONs were identified as the most effective therapeutic to treat AKI in mice, based on the PET analysis.

Yan and his colleagues prepared a series of DONs and used radio labeling to study their behavior in mouse kidney, using PET imaging. The PET scans showed that the DONs had preferentially accumulated in the kidneys of healthy mice as well as those with induced AKI. Of the three shapes used in the experiments, the rectangular DONs provided the greatest benefit in terms of protection and therapy and were comparable in their effect to the drug NAC, considered the gold standard treatment for AKI.

Patients with kidney disease often have accompanying maladies, including a high incidence of cardiovascular disease and malignancy. Acute kidney illness may be induced through the process of oxidative stress, which results from an increase in oxygen-containing waste products known as , that cause damage to lipids, proteins and DNA. This can occur when the delicate balance of free radicals and anti-oxidant defenses becomes destabilized, causing inflammation and accelerating the progression of renal disease. (Foods and supplements rich in antioxidants act to protect cells from the harmful effects of reactive oxygen species.)

Safeguarding kidneys with DNA geometry

The protective and therapeutic effects of the DONs described in the new study are due to the ability of the nanostructures to scavenge reactive oxygen species, thereby insulating vulnerable cells from damage due to oxidative stress. This effect was studied in human embryonic kidney cell lines as well as in living mice. The accumulation of the nanostructures in both healthy and diseased kidneys provided an increased therapeutic effect compared with traditional AKI therapy. (DONs alleviated oxidative stress within 2 hours of incubation with affected kidney cells.)

Improvement in AKI kidney function—comparable with high-dose administration of the drug NAC— was observed following the introduction of nanostructures. Examination of stained tissue samples further confirmed the beneficial effects of the DONs in the kidney.

The authors propose several mechanisms to account for the persistence in the kidneys of properly folded origami nanostructures, including their resistance to digestive enzymes, avoidance of immune surveillance and low protein absorption.

Levels of serum creatinine and blood urea nitrogen (BUN) were used to assess renal function in mice. AKI mice treated with rectangular DONs displayed improved kidney excretory function comparable to mice receiving treatment using the mainline drug NAC.

Further, the team established the safety of rectangular DONs, evaluating their potential to elicit an immune response in mice by examining blood levels of interleukin-6 and tumor necrosis factor alpha. Results showed the DONs were non-immunogenetic and tissue staining of heart, liver, spleen lungs and kidney revealed their low toxicity in primary organs, making them attractive candidates for clinical use in humans.

Based on the effective scavenging of reactive oxygen species by DONs in both human kidney cell culture and living mouse , the study concludes that the approach may indeed provide localized protection for kidneys from AKI and may even offer effective treatment for AKI-damaged kidneys or other renal disorders.

The successful proof-of-concept study expands the potential for a new breed of therapeutic programmable nanostructures, engineered to address far-flung medical challenges, from smart drug delivery to precisely targeted organ and tissue repair.

 Explore further: YAP after acute kidney injury

More information: Dawei Jiang et al, DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury, Nature Biomedical Engineering (2018). DOI: 10.1038/s41551-018-0317-8

 

Our Bioelectronic Future: Smaller, Smarter, Connected – De Lange Conference at Rice University: Video


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Bioelectronics, Our Bioelectronic Future: Smaller, Smarter, Connected

De Lange Conference XI | December 4-5, 2018 | Rice University De Lange Conference XI will bring together biologists, engineers, medical researchers, policy scholars, humanists, and industrial representatives from the nascent bioelectronics industry and federal agencies will serve to identify the grand challenges in the field, including technological, ethical, legal, and societal issues. The biennial De Lange Conferences, funded by the De Lange Endowment, were established by C.M. and Demaris Hudspeth in honor of Demaris’ parents, Albert and Demaris De Lange. For more information, visit delange.rice.edu

 

Read More About Graphene Applications for Bio-Electronics and Neuroprosthetics

Graphene Bioelectrics id50987_1The term bioelectronics, or bionics for short, describes a research field that is concerned with the integration of biological components with electronics; specifically, the application of biological materials and processes in electronics, and the use of electronic devices in living systems.
One day, bionics research could result in neural prostheses that augment or restore damaged or lost functions of the nervous system – restore vision, healing spinal cord injuries, and ameliorate neurodegenerative diseases such as Parkinson’s.

‘DNA-based’ nanocomposite hydrogel as a potent injectable drug delivery platform – A base matrix to form tissue engineering scaffolds and drug delivery platforms – U of Kansas


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DNA is the carrier of genetic information of all living beings on earth. The nitrogenous base sequences along the DNA chain are responsible for the encoding and transmission of genetic information.

DNA downloadRead More: Understanding DNA

Besides being a genetic material, DNA can also be considered as a chemical entity and hence can be exploited as a base matrix to form tissue engineering scaffolds and drug delivery platforms.
From a chemical perspective, DNA is a long chain polymer consisting of monomeric repeat units. Each repeat unit consists of a deoxyribose sugar molecule linked to a phosphate group. Every monomeric unit is also connected to one of the four nitrogenous bases.
The base pairing interactions between the DNA strands are highly specific. Together with the binding of other substances to the backbone, this can be exploited to construct three-dimensionally interconnected hydrogel networks.
Sayantani Basu, a PhD student from the lab of Professor Arghya Paul (BioIntel Research Group) at the University of Kansas, Lawrence, has been working on the utilization of DNA as a high molecular weight polymeric chain in order to form hydrogel networks for tissue regeneration and drug delivery applications.
They have designed shear thinning hydrogels, which can be passed through a 22-gauge syringe by taking advantage of the native chemical structure of DNA and its specific base pairing interactions.
“As a bio and nano-materials engineering lab we are constantly trying to explore the structural properties of different polymers and nanoparticles to design smart materials for diverse biomedical applications including regenerative medicine,” says Dr. Arghya Paul.
Previous studies from Paul’s BioIntel Research Group at the University of Kansas have shown the use of two-dimensional nanosilicates to form injectable hydrogels (Acta Biomaterialia“Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue”)..
In their recent study (ACS Nano“Harnessing the Noncovalent Interactions of DNA Backbone with 2D Silicate Nanodisks To Fabricate Injectable Therapeutic Hydrogels”), the group has investigated the potential of DNA to form self-assembled injectable hydrogels via physical crosslinking with silicate nanodisks.

 

DNA-based physically crosslinked hydrogels
DNA-based physically crosslinked hydrogels. (Reprinted with permission by American Chemical Society) (click on image to enlarge)
 

The DNA-nanosilicate hydrogel is formed by a combination of non-covalent network points without the need of any toxic chemical crosslinkers. DNA denaturation and rehybridization mechanism as well as attractive electrostatic interactions of nanosilicates with the DNA backbone are utilized to generate an interconnected network via a two-step gelation process.

Basu has also shown a sustained release of a model osteogenic drug dexamethasone from the nanoengineered hydrogels and confirmed the bioactivity of the released drugs under lab and preclinical settings to promote bone regeneration.
The animal work was done in collaboration with Professor Jinxi Wang, who directs the Harrington Laboratory for Molecular Orthopedics at University of Kansas Medical Center.
Future work from the research group will focus on the feasibility of the DNA based hydrogels for other more potent drug (small molecules, nucleic acids, growth factors) delivery, and cell delivery applications.
Provided by the University of Kansas as a Nanowerk exclusive.

Nanoparticle therapy could deliver double blow to cancer


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A new cancer therapy using nanoparticles to deliver a combination therapy direct to cancer cells could be on the horizon, thanks to research from the University of East Anglia.

The new , which has been shown to make breast  and prostate cancer tumours more sensitive to chemotherapy, is now close to entering clinical trials.

And scientists at UEA’s Norwich Medical School have confirmed that it can be mass-produced, making it a viable treatment if proved effective in human trials.

Using  to get drugs directly into a tumour is a growing area of cancer research. The technology developed at UEA is the first of its kind to use nanoparticles to deliver two drugs in combination to target .

The drugs, already approved for clinical use, are an anti-cancer drug called docetaxel, and fingolimod, a multiple sclerosis drug that makes tumours more sensitive to chemotherapy.

Fingolimod cannot currently be used in cancer treatment because it also supresses the immune system, leaving patients with dangerously low levels of .

And while docetaxel is used to treat many cancers, particularly breast, prostate, stomach, head and neck and some lung cancers, its toxicity can also lead to serious side effects for patients whose tumours are chemo-resistant.

Because the nanoparticles developed by the UEA team can deliver the drugs directly to the tumour site, these risks are vastly reduced. In addition, the targeted approach means less of the  is needed to kill off the cancer cells.

“So far nobody has been able to find an effective way of using fingolimod in cancer patients because it’s so toxic in the blood,” explains lead researcher, Dr. Dmitry Pshezhetskiy from the Norwich Medical School at UEA.

“We’ve found a way to use it that solves the toxicity problem, enabling these two drugs to be used in a highly targeted and powerful combination.”

The UEA researchers worked with Precision NanoSystems’ Formulation Solutions Team who used their NanoAssemblr technology to investigate if it was possible to synthesise the different components of the therapy at an industrial scale.

Following successful results on industrial scale production, and a published international patent application, the UEA team is now looking for industrial partners and licensees to move the research towards a phase one clinical trial.

Also included within the nanoparticle package are molecules that will show up on an MRI scan, enabling clinicians to monitor the spread of the particles through the body.

The team has already carried out trials in mice that show the therapy is effective in reducing breast and prostate tumours. These results were published in 2017.

“Significantly, all the components used in the therapy are already cleared for clinical use in Europe and the United States,” says Dr. Pshezhetskiy. “This paves the way for the next stage of the research, where we’ll be preparing the therapy for patient trials.”

“New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth,” by Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper and Dmitri Pchejetski was published in Breast Cancer Research and Treatment on 10 July 2017.

“Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of ,” by Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper and Dmitri Pchejetski was published in Scientific Reports on 19 July 2017.

 Explore further: Lipid molecules can be used for cancer growth

More information: Heba Alshaker et al. New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth, Breast Cancer Research and Treatment (2017). DOI: 10.1007/s10549-017-4380-8

Qi Wang et al. Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer, Scientific Reports (2017). DOI: 10.1038/s41598-017-06142-x

Read more at: https://phys.org/news/2018-08-nanoparticle-therapy-cancer.html#jCp

New Targeting strategy developed by Penn State may open door to better cancer drug delivery


Drug delivery targetingstrIn the transition from benign to malignant, cancer cells transition from stiff to soft. Mechanotargeting harnesses mechanics to improve targeting efficiency of nanparticle-based therapeutic agents. Credit: Zhang lab/vecteezy.com

Bioengineers may be able to use the unique mechanical properties of diseased cells, such as metastatic cancer cells, to help improve delivery of drug treatments to the targeted cells, according to a team of researchers at Penn State.

Many labs around the world are developing nanoparticle-based,  to selectively target tumors. They rely on a key-and-lock system in which protein keys on the surface of the nanoparticle click into the locks of a highly expressed protein on the surface of the cancer cell. The cell membrane then wraps around the nanoparticle and ingests it. If enough of the nanoparticles and their drug cargo is ingested, the cancer cell will die.

The adhesive force of the lock and key is what drives the nanoparticle into the cell, said Sulin Zhang, professor of engineering science and mechanics.

“It is almost universal that whenever there is a driving force for a process, there always is a resistive force,” Zhang said. “Here, the driving force is biochemical—the protein-protein interaction.”

The resistive force is the mechanical energy cost required for the membrane to wrap around the nanoparticle. Until now, bioengineers only considered the driving force and designed nanoparticles to optimize the chemical interactions, a targeting strategy called “chemotargeting.” Zhang believes they should also take into account the mechanics of the  to design nanoparticles to achieve enhanced targeting, which forms a new targeting strategy called “mechanotargeting.”

“These two targeting strategies are complementary; you can combine chemotargeting and mechanotargeting to achieve the full potential of nanoparticle-based diagnostic and therapeutic agents,” Zhang said. “The fact is that targeting efficiency requires a delicate balance between driving and resistive forces. For instance, if there are too many keys on the nanoparticle surface, even though these keys only weakly interact with the nonmatching locks on normal cells, these weak, off-target interactions may still provide enough adhesion energy for the nanoparticles to penetrate the  and kill the healthy cells.”

On the other hand, if the adhesion energy is not high enough, the nanoparticle won’t get into the cell.

In “Mechanotargeting: Mechanics-dependent Cellular Uptake of Nanoparticles,” published online ahead of print in the journal Advanced Materials, Zhang and the team report the results of experiments on cancer cells grown on hydrogels of variable stiffness. On soft hydrogels the cells remained cohesive and benign and experienced a nearly constant stress that limited the uptake of the nanoparticles. But on stiff hydrogels the cells became metastatic and adopted a three-dimensional shape, offering more surface area for nanoparticles to adhere, and became less stressed. Under this condition, the cells took up five times the number of nanoparticles as the benign cells.

“The nanoparticles are fluorescent, so we count the number of  that get into the cell by the fluorescence intensity. We found that in the malignant cells the intensity is five times higher,” Zhang said. “That proves that mechanotargeting works.”

 Explore further: Nanoparticle aggregates for destruction of cancer cells

More information: Qiong Wei et al, Mechanotargeting: Mechanics-Dependent Cellular Uptake of Nanoparticles, Advanced Materials (2018). DOI: 10.1002/adma.201707464

 

America’s National Laboratories – 75 Breakthroughs We’ve Made that You May Not have Read About


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America’s National Laboratories have been changing and improving the lives of millions of people for more than 75 years. Born at a time when the world faced a dire threat, the laboratories came together to advance science, safeguard the nation and protect our freedoms for generations to come. This network of Department of Energy Laboratories has grown into 17 facilities, working together as engines of prosperity and invention. As this list of breakthroughs attests, Laboratory discoveries have spawned industries, saved lives, generated new products, fired the imagination and helped to reveal the secrets of the universe. Rooted in the need to serve the public good and support the global community, the National Laboratories have put an American stamp on the last century of science. With equal ingenuity and tenacity, they are now engaged in innovating the future.

National Labs Map downloadDownload and read 75 Breakthroughs by America’s National Laboratories.

75 Breakthroughs

At America’s National Laboratories, we’ve …

Advanced supercomputing

The National Labs operate some of the most significant high performance computing resources available, including 32 of the 500 fastest supercomputers in the world. These systems, working at quadrillions of operations per second, model and simulate complex, dynamic systems – such as the nuclear deterrent – that would be too expensive, impractical or impossible to physically demonstrate. Supercomputers are changing the way scientists explore the evolution of our universe, climate change, biological systems, weather forecasting and even renewable energy.

Decoded DNA 

In 1990, the National Labs joined with the National Institutes of Health and other laboratories to kick off the Human Genome Project, an international collaboration to identify and map all of the genes of the human genome.

Brought the web to the United States 

National Lab scientists, seeking to share particle physics information, were first to install a web server in North America, kick-starting the development of the worldwide web as we know it.

Put eyes in the sky 

Vela satellites, first launched in 1963 to detect potential nuclear detonations, transformed the nascent U.S. space program. The satellites featured optical sensors and data processing, logic and power subsystems designed and created by National Labs.

Revolutionized medical diagnostics and treatment 

Researchers at the National Labs helped to develop the field of nuclear medicine, producing radioisotopes to diagnose and treat disease, designing imaging technology to detect cancer and developing software to target tumors while sparing healthy tissue.

Powered NASA spacecraft 

The National Labs built the enclosure for the radioisotope thermoelectric generators that fuel crafts such as Cassini and have begun producing plutonium-238 for future NASA missions.

Harnessed the power of the atom 

National Lab scientists and engineers have led the world in developing safe, efficient and emissions-free nuclear power. Starting with the first nuclear reactor to generate electricity, National Labs have been the innovation engine behind the peaceful use of nuclear energy. Today’s labs are supporting the next generation of nuclear power that will be available for the nation and world.

Brought safe water to millions 

Removing arsenic from drinking water is a global priority. A long-lasting particle engineered at a National Lab can now do exactly that, making contaminated water safe to drink. Another technology developed at a National Lab uses ultraviolet light to kill water-borne bacteria that cause dysentery, thus reducing child mortality in the developing world.

Filled the Protein Data Bank 

National Lab X-ray facilities have contributed a large portion of more than 100,000 protein structures in the Protein Data Bank. A protein’s structure reveals how it functions, helping scientists understand how living things work and develop treatments for disease. Almost all new medications that hit the market start with these data bank structures.

Invented new materials 

National Labs provide the theory, tools and techniques that offer industry revolutionary materials such as strong, lighter-weight metals and alloys that save fuel and maintenance costs and enable cleaner, more efficient engines.

Found life’s mystery messenger 

National Lab scientists discovered how genetic instructions are carried to the cell’s protein manufacturing center, where all of life’s processes begin. Subsequent light source research on the genetic courier, called messenger RNA, has revealed how the information is transcribed and how mistakes can cause cancer and birth defects.

Mapped the universe — and the dark side of the moon

Credit for producing 3D maps of the sky — and 400 million celestial objects — goes to National Lab scientists, who also developed a camera that mapped the entire surface of the moon.

Shed light on photosynthesis 

Ever wonder how plants turn sunlight into energy? National Lab scientists determined the path of carbon through photosynthesis, and today use X-ray laser technology to reveal how each step in the process is triggered by a single particle of light. This work helps scientists explore new ways to get sustainable energy from the sun.

Solved cultural mysteries 

The works of ancient mathematician Archimedes — written over by medieval monks and lost for millennia — were revealed to modern eyes thanks to the X-ray vision and light-source technology at National Labs. These studies also have revealed secrets of masterpiece paintings, ancient Greek vases and other priceless cultural artifacts.

Revolutionized accelerators 

A National Lab built and operated the first large-scale accelerator based on superconducting radio frequency technology. This more efficient technology now powers research machines for exploring the heart of matter, examining the properties of materials and providing unique information about the building blocks of life.

Los Alamos 1200px-Los_Alamos_aerial_viewRevealed the secrets of matter 

Protons and neutrons were once thought to be indivisible. National Lab scientists discovered that protons and neutrons were made of even smaller parts, called quarks. Over time, experimenters identified six kinds of quarks, three types of neutrinos and the Higgs particle, changing our view of how the material world works.

Confirmed the Big Bang and discovered dark energy

National Lab detectors aboard a NASA satellite revealed the birth of galaxies in the echoes of the Big Bang. Dark energy — the mysterious something that makes up three-quarters of the universe and causes it to expand at an accelerating rate — also was discovered by National Lab cosmologists.

Discovered 22 elements 

The periodic table would be smaller without the National Labs. To date the National Labs have discovered: technetium, promethium, astatine, neptunium, plutonium, americium, curium, berkelium, californium, einsteinium, fermium, mendelevium, nobelium, lawrencium, rutherfordium, dubnium, seaborgium, flerovium, moscovium, livermorium, tennessine and oganesson.

Made refrigerators cool 

Next-generation refrigerators will likely put the freeze on harmful chemical coolants in favor of an environmentally friendly alloy, thanks to National Lab scientists.

Got the lead out 

Removing hazardous lead-based solders from the environment is a reality thanks to a lead-free alloy of tin-silver-copper developed at a National Lab. The lead-free solder has been licensed by more than 60 companies worldwide.

Invented a magic sponge to clean up oil spills

National Lab scientists used a nano technique to invent a new sponge that can absorb 90 times its own weight in oil from water. It can be wrung out to collect the oil and reused hundreds of times — and it can collect oil that has sunk below the surface, something previous technology couldn’t do.

Added the punch to additive manufacturing 

High-pressure gas atomization processing pioneered at a National Lab made possible the production of titanium and other metal-alloy powders used in additive manufacturing and powder metallurgy.

 

Created inexpensive catalysts 

Low-cost catalysts are key to efficient biomass refining. National Lab scientists created catalysts that are inexpensive and stable for biomass conversion. ANL_H_White

Created high-tech coatings to reduce friction 

National Lab scientists created ways to reduce wear and tear in machines from table fans to car engines all the way up to giant wind turbines, such as a diamond-like film that rebuilds itself as soon as it begins to break down — so that engines last longer and need fewer oil additives.

Put the jolt in the Volt 

Chevy’s Volt would not be able to cruise on battery power were it not for the advanced cathode technology that emerged from a National Lab. The same technology is sparking a revival of America’s battery manufacturing industry.

Cemented a new material 

National Lab scientists have developed a novel and versatile material that blends properties of ceramic and concrete to form a non-porous product that can do everything from seal oil w ells to insulate walls with extra fire protection. It even sets in cold weather.

Pioneered efficient power lines 

New kinds of power lines made from superconductors can carry electric current with no energy loss. Now deployed by National Lab scientists, these prototypes could usher in a new era of ultra-efficient power transmission.

Made early universe quark soup 

National Lab scientists used a particle collider to recreate the primordial soup of subatomic building blocks that last existed shortly after the Big Bang. The research is expanding scientists’ understanding of matter at extreme temperatures and densities.

Oak Ridge NL DWKcxYZXkAEY9NVLevitated trains with magnets 

Say goodbye to traffic jams. National Lab scientists developed a technology that uses the attractive and repulsive forces of magnets to levitate and propel trains. Maglev trains now ferry commuters in Japan and China and will be operational in other countries soon.

Developed efficient burners 

National Lab researchers developed cleaner-combusting oil burners, saving consumers more than $25 billion in fuel costs and keeping more than 160 megatons of carbon dioxide out of Earth’s atmosphere.

Improved automotive steel

A company with National Lab roots is pioneering a metal that weighs significantly less than regular steel, retains steel’s strength and malleability and can be fabricated without major modifications to the automotive manufacturing infrastructure.

Looked inside weapons

National Lab researchers created a device that could identify the contents of suspicious chemical and explosive munitions and containers, while minimizing risk to the people involved. The technology, which quickly identifies the chemical makeup of weapons, has been used to verify treaties around the world.

Pioneered nuclear safety modeling 

National Lab scientists began developing the Reactor Excursion and Leak Analysis Program (RELAP) to model nuclear reactor coolant and core behavior. Today, RELAP is used throughout the world and has been licensed for both nuclear and non-nuclear applications, including modeling of jet aircraft engines and fossil-fuel power plant components.

Identified good and bad cholesterol 

The battle against heart disease received a boost in the 1960s when National Lab research unveiled the good and bad sides of cholesterol. Today, diagnostic tests that detect both types of cholesterol save lives.

Unmasked a dinosaur killer 

Natural history’s greatest whodunit was solved in 1980 when a team of National Lab scientists pinned the dinosaurs’ abrupt extinction on an asteroid collision with Earth. Case closed.

Pitted cool roofs against carbon dioxide 

National Lab researchers and policy experts led the way in analyzing and implementing cool roofing materials, which reflect sunlight, lower surface temperature and slash cooling costs.

Squeezed fuel from microbes 

In a milestone that brings advanced biofuels one step closer to America’s gas tanks, National Lab scientists helped develop a microbe that can produce fuel directly from biomass.

Tamed hydrogen with nanoparticles 

To replace gasoline, hydrogen must be safely stored and easy to use, which has proven elusive. National Lab researchers have now designed a new pliable material using nanoparticles that can rapidly absorb and release hydrogen without ill effects, a major step in making fuel-cell powered cars a commercial reality.

Exposed the risk 

You can sleep easier thanks to National Lab research that quantified the health risk posed by radon gas in parts of the country. Subsequent EPA standards, coupled with radon detection and mitigation measures pioneered by a National Lab research team, prevent the naturally occurring gas from seeping into basements, saving thousands of lives every year.

Created a pocket-sized DNA sampler 

A tool that identifies the microbes in air, water and soil samples is fast becoming a workhorse in public health, medical and environmental cleanup projects. Developed by National Lab scientists, the credit-card-sized device pinpoints diseases that kill coral reefs and catalogs airborne bacteria over U.S. cities. It also was used to quickly categorize the oil-eating bacteria in the plumes of the Deepwater Horizon spill.

Fabricated the smallest machines

The world’s smallest synthetic motors — as well as radios, scales and switches that are 100,000 times finer than a human hair — were engineered at a National Lab. These and other forays into nanotechnology could lead to life-saving pharmaceuticals and more powerful computers.

Preserved the sounds of yesteryear 

National Lab scientists engineered a high-tech way to digitally reconstruct aging

sound recordings that are too fragile to play, such as Edison wax cylinders from the late 1800s. Archivists estimate that many of the millions of recordings in the world’s sound archives, including the U.S. Library of Congress, could benefit from the technology.

Exposed explosives 

A credit-card sized detector developed by National Lab scientists can screen for more than 30 kinds of explosives in just minutes. The detector, called ELITE, requires no po wer and is widely used by the military, law enforcement and security personnel.

Toughened airplanes 

A National Lab and industry technique for strengthening metal by bombarding it with laser pulses has saved the aircraft industry hundreds of millions of dollars in engine and aircraft maintenance expenses.

Simulated reality 

Trains, planes and automobiles — and thousands of other objects — are safer, stronger and better-designed thanks to computer simulation software, DYNA 3D, developed by National Lab researchers.

Detected the neutrino 

Starting with the Nobel-Prize winning discovery of the neutrino in 1956 by Fred Reines and Clyde Cowan Jr., National Lab researchers have made numerous contributions to neutrino physics and astrophysics.

Discovered gamma ray bursts

Sensors developed at the National Labs and placed aboard Vela satellites were used in the discovery of gamma-ray bursts (GRBs) in 1973. GRBs are extremely energetic explosions from distant galaxies. Scientists believe that most of these bursts consist of a narrow beam of intense radiation released when a rapidly rotating, high-mass star collapses to form a neutron star, a quark star or a black hole.

Created the first 100-Tesla magnetic field 

National Lab scientists achieved a 100.75-Tesla magnetic pulse in March 2012, setting a world record. The pulse was nearly 2 million times more powerful than Earth’s magnetic field. The 100-Tesla multi-shot magnet can be used over and over again without being destroyed by the force of the field it creates, and produces the most powerful non-destructive magnetic field in the world.

Froze smoke for hot uses 

National Labs researchers perfected aerogels, known as frozen smoke. They are one of the lightest solids ever made and have the highest heat resistance of any material tested. They also are fireproof and extraordinarily strong — able to support more than a thousand times their own weight. As a result of their heat resistance, aerogels are outstanding candidates for insulation in buildings, vehicles, filters and appliances.

Invented the cell sorter 

During the 1960s, a National Lab physicist invented a “cell sorter” — a novel device that works much like an ink jet printer, guiding a tiny flow of cell-containing droplets so cells of interest can be deflected for counting and study. Cell sorters are a vital tool for studying the biochemistry behind many diseases, including cancer and AIDS.

Ushered a domestic energy renaissance 

National Lab research jump-started the shale gas revolution by pointing the way to key technologies and methodologies for cost efficient extraction. An estimated $220 million in research and development expenditures on unconventional gas R&D from 1976 to 1992 have resulted in an estimated $100 billion in annual economic activity from shale gas production alone.

Enabled space exploration 

National Labs invented Laser-Induced Breakdown Spectroscopy (LIBS), the backbone of the device that allowed the Curiosity Rover to analyze material from Mars. Lab researchers also found the right combination of materials to make high-efficiency solar cells for spacecraft.

Sharply curtailed power plant air emissions 

National Lab scientists introduced some 20 innovative technologies — such as low nitrogen oxide (NOx) burners, flue gas desulfurization (scrubbers) and fluidized bed combustion — through the Clean Coal Technology Development Program that have deeply penetrated the marketplace, substantially controlled harmful power plant emissions and benefited energy production and air quality.

Made wind power mainstream 

Increasing wind turbine efficiency with high efficiency airfoils has reduced the cost of wind power by more than 80 percent over the last 30 years. Now deployed in wind farms nationwide, these turbines owe their existence to National Lab research.

Engineered smart windows 

National Lab scientists have created highly insulated windows that change color to modulate interior temperatures and lighting. If broadly installed, they could save about 5 percent of the nation’s total energy budget.

Delivered troops safely 

National Lab researchers have developed computer models that effectively manage the complex logistical tasks of deploying troops and equipment to distant destinations.

Channeled chips and hips 

Integrated circuits and artificial hips owe their success to a National Lab discovery that revealed how to change a material by injecting it with charged atoms, called ions. Ion channeling is now standard practice in industry and science.

Made 3D printing bigger and better 

A large-scale additive manufacturing platform developed by a National Lab and an industry partner printed 3D components 10 times larger and 200 times faster than previous processes. So far, the system has produced a 3D-printed sports car, SUV, house, excavator and aviation components.

Purified vaccines

National Lab researchers adapted nuclear separations technology to develop a zonal centrifuge used to purify vaccines, which reduces or eliminates unwanted side effects. Commercial centrifuges based on the invention produce vaccines for millions of people.

Built a better building 

A National Lab has built one of the world’s most energy efficient office buildings. The facility, operating as a living laboratory at a lab site, uses 50 percent less energy than required by commercial codes and only consumes energy produced by renewable power on or near the building.

Improved airport security 

Weapons, explosives, plastic devices and other concealed tools of terrorists are easier to detect thanks to technology developed at a National Lab and now installed in airports worldwide.

Improved grid resiliency 

A National Lab created an advanced battery that can store large amounts of energy from intermittent renewable sources — such as wind and solar — onto the power grid, while also smoothing over temporary disruptions to the grid. Several companies have licensed the technology and offer it as a commercial product.

Solved a diesel dilemma 

A National Lab insight into how catalysts behave paved the way for a new, “lean-burn” diesel engine that met emissions standards and improved fuel efficiency by 25 percent over conventional engines.

Harvested energy from air 

A miniature device — commercialized by private industry after a National Lab breakthrough — generates enough power from small temperature changes to power wireless sensors or radio frequency transmitters at remote sites, such as dams, bridges and pipelines.

Gone grid friendly 

Regulating the energy use of household appliances — especially at peak times — could slash energy demand and avoid blackouts. A National Lab appliance-control device senses grid stress and responds instantly to turn off machines and reduce end-use demand, balancing the system so that the power stays on.

Put the digital in DVDs 

The optical digital recording technology behind music, video and data storage originated at a National Lab nearly 40 years ago.

Locked nuclear waste in glass 

Disposal of U.S. Cold War waste is safer thanks to National Lab scientists who developed and deployed a process to lock it into glass to keep it from leaching into the environment.

Cleaned up anthrax 

Scientists at a National Lab developed a non-toxic foam that neutralizes chemical and biological agents. This foam was used to clean up congressional office buildings and mail rooms exposed to anthrax in 2001.

Removed radiation from Fukushima seawater 

After a tsunami damaged the Fukushima Daiichi nuclear power plant in 2011, massive amounts of seawater cooled the reactor. A molecular sieve engineered by National Lab scientists was used to extract radioactive cesium from tens of millions of gallons of seawater.11

Sped up Ebola detection 

In 2014, researchers from a National Lab modeled the Liberian blood sample transport system and made recommendations to diagnose patients quicker. This minimized the amount of time people were waiting together, reducing the spread of Ebola.

Prevented unauthorized use of a nuclear weapon 

In 1960, National Lab scientists invented coded electromechanical locks for all U.S. nuclear weapons. The switch blocks the arming signal until it receives the proper presidential authorization code.

Launched the LED lighting revolution 

In the 1990s, scientists at a National Lab saw the need for energy-efficient solid-state lighting and worked with industry to develop white LEDs. Today, white LEDs are about 30 percent efficient, with the potential to reach 70 percent to 80 percent efficiency. Fluorescent lighting is about 20 percent efficient and incandescent bulbs are 5 percent.

Mastered the art of artificial photosynthesis 

National Lab scientists engineered and synthesized multi-layer semiconductor structures in devices that directly convert sunlight to chemical energy in hydrogen by splitting water at efficiencies greater than 15 percent. This direct conversion of sunlight to fuels paves the way for use of solar energy in applications beyond the electrical grid.

Advanced fusion technology

From the first fusion test reactor to briefly produce power at the megawatt scale, and the world’s largest and most energetic laser creating extreme conditions mimicking the Big Bang, the interiors of planets and stars and thermonuclear weapons, to the international experiment to generate industrial levels of fusion energy from burning plasmas, fusion science and applications are advancing because of the National Labs.

Made the first molecular movie 

National Lab scientists have used ultrafast X-rays to capture the first molecular movies in quadrillionths-of-a-second frames. These movies detail the intricate structural dances of molecules as they undergo chemical reactions.

DOE imagesThe National Laboratory System: Protecting America Through Science and Technology

For more than 75 years, the Department of Energy’s National Laboratories have solved important problems in science, energy and national security. This expertise keeps our nation at the forefront of science and technology in a rapidly changing world. Partnering with industry and academia, the laboratories also drive innovation to advance economic competitiveness and     ensure our nation’s future prosperity.

Novel Nanomedicine Inhibits Progression of Pancreatic Cancer in Mice – Tel Aviv University


Nanomedicine I download

Survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumor suppressant, Tel Aviv University researchers say

A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene — a gene that promotes the development of cancer — and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.

Nanomedicine III imagesThe study, which was published in Nature Communications, was led by Prof. Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr. Shay Eliyahu, both of Prof. Satchi-Fainaro’s multidisciplinary laboratory, in collaboration with Prof. Eytan Ruppin of TAU’s Computer Science Department and the University of Maryland and Prof. Iris Barshack and Dr. Talia Golan of Chaim Sheba Medical Center, Tel Hashomer.

Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within just a year of diagnosis. “Despite all the treatments afforded by modern medicine, some 75% of all pancreatic cancer patients die within 12 months of diagnosis, including many who die within just a few months,” Prof. Satchi-Fainaro says.

“But around seven percent of those diagnosed will survive more than five years. We sought to examine what distinguishes the survivors from the rest of the patients,” Prof. Satchi-Fainaro continues. “We thought that if we could understand how some people live several years with this most aggressive disease, we might be able to develop a new therapeutic strategy.”

Nanomedicine I downloadCalling a nano-taxi

The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumor suppressant, and PLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation made sense for such an aggressive cancer. But the team needed to see if the same was true in humans.

The scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients. The molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer.

The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues.

“We designed a nanocarrier to deliver two passengers: (1) miR-34a, which degrades hundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), that silences a single gene,” Prof. Satchi-Fainaro says. “These were delivered directly to the tumor site to change the molecular signature of the cancer cells, rendering the tumor dormant or eradicating it altogether.Nanomedicine II pancreatic-cancer-1140x641

“The nanoparticle is like a taxi carrying two important passengers,” Prof. Satchi-Fainaro continues. “Many oncology protocols are cocktails, but the drugs usually do not reach the tumor at the same time. But our ‘taxi’ kept the ‘passengers’ — and the rest of the body — safe the whole way, targeting only the tumor tissue. Once it ‘parked,’ an enzyme present in pancreatic cancer caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address — the tumor cells.”

Improving the odds

To validate their findings, the scientists injected the novel nanoparticles into pancreatic tumor-bearing mice and observed that by balancing these two targets — bringing them to a normal level by increasing their expression or blocking the gene responsible for their expression — they significantly prolonged the survival of the mice.

“This treatment takes into account the entire genomic pattern, and shows that affecting a single gene is not enough for the treatment of pancreatic cancer or any cancer type in general,” according to Prof. Satchi-Fainaro.

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Research for the study was funded by the European Research Council (ERC), Tel Aviv University’s Cancer Biology Research Center (CBRC) and the Israel Science Foundation (ISF).

American Friends of Tel Aviv University (AFTAU) supports Israel’s most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. For three years in a row, TAU ranked 9th in the world, and first in Israel, for alumni going on to become successful entrepreneurs backed by significant venture capital, a ranking that surpassed several Ivy League universities. To date, 2,400 patents have been filed out of the University, making TAU 29th in the world for patents among academic institutions.

Light-activated Nanoparticles (Quantum Dots) can supercharge current antibiotics


QDs and Antibiotics CU 171004142650_1_540x360CU Boulder researcher Colleen Courtney (left) speaks with Assistant Professor Anushree Chatterjee (right) inside a lab in the BioFrontiers Institute.
Credit: University of Colorado Boulder

Light-activated nanoparticles, also known as quantum dots, can provide a crucial boost in effectiveness for antibiotic treatments used to combat drug-resistant superbugs such as E. coliand Salmonella, new University of Colorado Boulder research shows.

Multi-drug resistant pathogens, which evolve their defenses faster than new antibiotic treatments can be developed to treat them, cost the United States an estimated $20 billion in direct healthcare costs and an additional $35 billion in lost productivity in 2013.

CU Boulder researchers, however, were able to re-potentiate existing antibiotics for certain clinical isolate infections by introducing nano-engineered quantum dots, which can be deployed selectively and activated or de-activated using specific wavelengths of light.

Rather than attacking the infecting bacteria conventionally, the dots release superoxide, a chemical species that interferes with the bacteria’s metabolic and cellular processes, triggering a fight response that makes it more susceptible to the original antibiotic.

“We’ve developed a one-two knockout punch,” said Prashant Nagpal, an assistant professor in CU Boulder’s Department of Chemical and Biological Engineering (CHBE) and the co-lead author of the study. “The bacteria’s natural fight reaction [to the dots] actually leaves it more vulnerable.”

The findings, which were published today in the journal Science Advances, show that the dots reduced the effective antibiotic resistance of the clinical isolate infections by a factor of 1,000 without producing adverse side effects.

“We are thinking more like the bug,” said Anushree Chatterjee, an assistant professor in CHBE and the co-lead author of the study. “This is a novel strategy that plays against the infection’s normal strength and catalyzes the antibiotic instead.”

While other previous antibiotic treatments have proven too indiscriminate in their attack, the quantum dots have the advantage of being able to work selectively on an intracellular level. Salmonella, for example, can grow and reproduce inside host cells. The dots, however, are small enough to slip inside and help clear the infection from within.

“These super-resistant bugs already exist right now, especially in hospitals,” said Nagpal. “It’s just a matter of not contracting them. But they are one mutation away from becoming much more widespread infections.”

Overall, Chatterjee said, the most important advantage of the quantum dot technology is that it offers clinicians an adaptable multifaceted approach to fighting infections that are already straining the limits of current treatments.

“Disease works much faster than we do,” she said. “Medicine needs to evolve as well.”

Going forward, the researchers envision quantum dots as a kind of platform technology that can be scaled and modified to combat a wide range of infections and potentially expand to other therapeutic applications.

Story Source:

Materials provided by University of Colorado at Boulder. Original written by Trent Knoss. Note: Content may be edited for style and length.


Journal Reference:

  1. Colleen M. Courtney, Samuel M. Goodman, Toni A. Nagy, Max Levy, Pallavi Bhusal, Nancy E. Madinger, Corrella S. Detweiler, Prashant Nagpal, and Anushree Chatterjee. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generationScience Advances, 04 Oct 2017 DOI: 10.1126/sciadv.1701776