New ‘Recipe’ To Produce Easily Nanoparticles

In a rare move, a Houston Methodist researcher is sharing his recipe for a new, more affordable way to make nanoparticles. This will empower any laboratory in the world to easily create similar nanoparticles and could lead to a whole new way of delivering biotherapeutic drugs and do it more quickly.

We’re the only lab in the world doing this,” said Ennio Tasciotti, Ph.D., director of the Center for Biomimetic Medicine at the Houston Methodist Research Institute and corresponding author on a paper published in Advanced Materials. “There are several questions about how our system works, and I can’t answer all of them. By giving away the so-called ‘recipe’ to make biomimetic nanoparticles, a lot of other labs will be able to enter this field and may provide additional solutions and applications that are beyond the reach of only one laboratory. You could say it’s the democratization of nanotechnology.

In the article, Tasciotti and his colleagues show how to standardize nanoparticle production to guarantee stability and reproducibility, while increasing yield. Eliminating the need for multi-million-dollar facilities, Tasciotti and his team demonstrate this using a readily available and relatively affordable piece of benchtop equipment to manufacture nanoparticles in a controlled, adjustable and low-cost manner.

Nanoparticles are generally made through cryptic protocols, and it’s very often impossible to consistently or affordably reproduce them,” Tasciotti added. “You usually need special, custom-made equipment or procedures that are available to only a few laboratories. We provide step-by-step instructions so that now everybody can do it.”


Effective Insertion Of DNA Molecules Into Cells For Gene Therapies

For years, researchers have attempted to harness the full potential of gene therapy, a technique that inserts genes into a patient’s cells to treat aggressive diseases such as cancer. But getting engineered DNA molecules into cells is not an easy task.

J. Mark Meacham, assistant professor of mechanical engineering & materials science at Washington University in St. Louis, leads a team of researchers that has developed a method enabling effective insertion of large molecules — such as DNA, RNA and proteins into cells and propels them into the cell nucleus. By combining a technique known as Acoustic Shear Poration (ASP) with electrophoresis, the approach uses ultrasound waves and focused mechanical force to create nanoscale holes, or pores, in the cell membrane that are big enough for large macromolecules or nanoparticles to pass into the cell’s interior.

Operation of the acoustic shear poration (ASP) device in Meacham’s lab

The researchers wrote that so far, ASP has achieved greater than 75 percent delivery efficiency of macromolecules. DNA insertion, or transfection, which is of most interest in gene therapy, is significantly more challenging. Yet the combined application of mechanical and electrical forces pioneered by Meacham and colleagues yields roughly 100 percent improvement in transfection versus pure mechanoporation. Results of the research are published in Scientific Reports.


Electronics: Printing of flexible, stretchable silver nanowire circuits

Researchers at North Carolina State University ( NC State) have developed a new technique that allows them to print circuits on flexible, stretchable substrates using silver nanowires. The advance makes it possible to integrate the material into a wide array of electronic devices.

Silver nanowires have drawn significant interest in recent years for use in many applications, ranging from prosthetic devices to wearable health sensors, due to their flexibility, stretchability and conductive properties. While proof-of-concept experiments have been promising, there have been significant challenges to printing highly integrated circuits using silver nanowires. Silver nanoparticles can be used to print circuits, but the nanoparticles produce circuits that are more brittle and less conductive than silver nanowires. But conventional techniques for printing circuits don’t work well with silver nanowires; the nanowires often clog the printing nozzles.

Our approach uses electrohydrodynamic printing, which relies on electrostatic force to eject the ink from the nozzle and draw it to the appropriate site on the substrate,” says Jingyan Dong, co-corresponding author of a paper on the work and an associate professor in NC State’s Edward P. Fitts Department of Industrial & Systems Engineering. “This approach allows us to use a very wide nozzle – which prevents clogging – while retaining very fine printing resolution.” “And because our ‘ink’ consists of a solvent containing silver nanowires that are typically more than 20 micrometers long, the resulting circuits have the desired conductivity, flexibility and stretchability,” says Yong Zhu, a professor of mechanical engineering at NC State and co-corresponding author of the paper.

In addition, the solvent we use is both nontoxic and water-soluble,” says Zheng Cui, a Ph.D. student at NC State and lead author of the paper. “Once the circuit is printed, the solvent can simply be washed off.” What’s more, the size of the printing area is limited only by the size of the printer, meaning the technique could be easily scaled up.

The researchers have used the new technique to create prototypes that make use of the silver nanowire circuits, including a glove with an internal heater and a wearable electrode for use in electrocardiography. NC State has filed a provisional patent on the technique.


Magnet-based Drug Delivery SystemTo Fight Cancer

A team of researchers at the University of Georgia (UGA)  has developed a non-invasive method of delivering drugs directly to cancerous tissue using magnetic forces, a form of treatment that could significantly reduce the toxic side effects of chemotherapy.

We showed that we can deliver anti-cancer drugs exactly in the area where they are needed and they can kill cancer cells,” said Andrey Zakharchenko, a graduate student in the Nanostructured Materials Lab in the UGA College of Family and Consumer Sciences who led the study.

The researchers from UGA and Clarkson University in New York first created very fine nanoparticles that acted as drug carriers, one a substrate base carrying the drugs, and the other loaded with enzymes.

Upon application of a relatively weak magnetic field, the two nanoparticles merge, forcing a reaction that releases the drugs at a specific location. By controlling the timing of the interaction, researchers could pinpoint delivery of the drug to a precise location, thus preventing side common side effects of chemotherapy, such as hair loss or cardiac toxicity. Researchers performed the proof of concept study in vitro using chemotherapy drugs and cancer cells. The next step would be to develop an animal model, Zakharchenko said.

The use of a static magnetic field to cause the reaction is important because it poses no threat to the body, said Sergiy Minko, the Georgia Power Professor of Fiber and Polymer Science within the FACS department of textiles, merchandising and interiors and the Franklin College of Arts and Sciences department of chemistry.

The article appears in the January issue of the journal Nature Catalysis


Self-regulating Nanoparticles Treat Cancer

Scientists from the University of Surrey have developed ‘intelligentnanoparticles which heat up to a temperature high enough to kill cancerous cells – but which then self-regulate and lose heat before they get hot enough to harm healthy tissue. The self-stopping nanoparticles could soon be used as part of hyperthermic-thermotherapy to treat patients with cancer, according to an exciting new study reported in NanoscaleThermotherapy has long been used as a treatment method for cancer, but it is difficult to treat patients without damaging healthy cells. However, tumour cells can be weakened or killed without affecting normal tissue if temperatures can be controlled accurately within a range of 42°C to 45°C.

Scientists from Surrey’s Advanced Technology Institute have worked with colleagues from the Dalian University of Technology in China to create nanoparticles which, when implanted and used in a thermotherapy session, can induce temperatures of up to 45°C. The Zn-Co-Cr ferrite nanoparticles produced for this study are self-regulating, meaning that they self-stop heating when they reach temperatures over 45°C. Importantly, the nanoparticles are also low in toxicity and are unlikely to cause permanent damage to the body.

This could potentially be a game changer in the way we treat people who have cancer. If we can keep cancer treatment sat at a temperature level high enough to kill the cancer, while low enough to stop harming healthy tissue, it will prevent some of the serious side effects of vital treatment. It’s a very exciting development which, once again, shows that the University of Surrey research is at the forefront of nanotechnologies – whether in the field of energy materials or, in this case, healthcare,” said Professor Ravi Silva, Head of the Advanced Technology Institute at the University of Surrey.

Dr. Wei Zhang, Associate Professor from Dalian University of Technology explains: “Magnetic induced hyperthermia is a traditional route of treating malignant tumours. However, the difficulties in temperature control has significantly restricted its usage If we can modulate the magnetic properties of the nanoparticles, the therapeutic temperature can be self-regulated, eliminating the use of clumsy temperature monitoring and controlling systems.

“By making magnetic materials with the Curie temperature falling in the range of hyperthermia temperatures, the self-regulation of therapeutics can be achieved. For the most magnetic materials, however, the Curie temperature is much higher than the human body can endure. By adjusting the components as we have, we have synthesized the nanoparticles with the Curie temperature as low as 34oC. This is a major nanomaterials breakthrough.”


One-Two Knockout Punch To Eradicate Super Bugs

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. coli and Salmonella, new CU 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. 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.”

We are thinking more like the bug,” explains 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.” The dots reduced the effective antibiotic resistance of the clinical isolate infections by a factor of 1,000 without producing adverse side effects.

The findings have been published today in the journal Science Advances.


Skin Patches Melt Fat

Researchers have devised a medicated skin patch that can turn energy-storing white fat into energy-burning brown fat locally while raising the body’s overall metabolism. The patch could be used to burn off pockets of unwanted fat such as “love handles” and treat metabolic disorders, such as obesity and diabetes, according to researchers at Columbia University Medical Center (CUMC) and the University of North Carolina. Humans have two types of fat. White fat stores excess energy in large triglyceride droplets. Brown fat has smaller droplets and a high number of mitochondria that burn fat to produce heat. Newborns have a relative abundance of brown fat, which protects against exposure to cold temperatures. But by adulthood, most brown fat is lost.

For years, researchers have been searching for therapies that can transform an adult’s white fat into brown fat—a process named browning—which can happen naturally when the body is exposed to cold temperatures—as a treatment for obesity and diabetes.


There are several clinically available drugs that promote browning, but all must be given as pills or injections,” said study co-leader Li Qiang, PhD, assistant professor of pathology & cell biology at Columbia. “This exposes the whole body to the drugs, which can lead to side effects such as stomach upset, weight gain, and bone fractures. Our skin patch appears to alleviate these complications by delivering most drugs directly to fat tissue.

To apply the treatment, the drugs are first encased in nanoparticles, each roughly 250 nanometers (nm) in diameter—too small to be seen by the naked eye. (In comparison, a human hair is about 100,000 nm wide.) The nanoparticles are then loaded into a centimeter-square skin patch containing dozens of microscopic needles. When applied to skin, the needles painlessly pierce the skin and gradually release the drug from nanoparticles into underlying tissue.

The findings, from experiments in mice, were published online today in ACS Nano.


Magnetic Cellular ‘Legos’ For Tissue Engineering

By incorporating magnetic nanoparticles in cells and developing a system using miniaturized magnets, researchers from 3 associated universities* in Paris (France) , have succeeded in creating cellular magneticLegos.” They were able to aggregate cells using only magnets and without an external supporting matrix, with the cells then forming a tissue that can be deformed at will. This approach, which is detailed in Nature Communications, could prove to be a powerful tool for biophysical studies, as well as the regenerative medicine of tomorrow.

Nanotechnology has quickly swept across the medical field by proposing sometimes unprecedented solutions at the furthest limits of current treatments, thereby becoming central to diagnosis and therapy, notably for the regeneration of tissue. A current challenge for regenerative medicine is to create a cohesive and organized cellular assembly without using an external supporting matrix. This is a particularly substantial challenge when it involves synthesizing thick and/or large-sized tissue, or when these tissues must be stimulated like their in vivo counterparts (such as cardiac tissue or cartilage) in order to improve their functionality.

The researchers met this challenge by using magnetism to act on the cells at a distance, in order to assemble, organize, and stimulate them. Cells, which are the building blocks of tissue, are thus magnetized in advance through the incorporation of magnetic nanoparticles, thus becoming true cellular magnetic “Legos” that can be moved and stacked using external magnets. In this new system acting as a magnetic tissue stretcher, the magnetized cells are trapped on a first micromagnet, before a second, mobile magnet traps the aggregate formed by the cells. The movement of the two magnets can stretch or compress the resulting tissue at will.

Researchers first used embryonic stem cells to test their system. They began by showing that the incorporation of nanoparticles had no impact on either the functioning of the stem cell or its capacity for differentiation. These functional magnetic stem cells were then tested in the stretcher, in which they remarkably differentiated toward cardiac cell precursors when stimulation imposed “magnetic beating” imitating the contraction of the heart. These results demonstrate the role that purely mechanical factors can play in cell differentiation.

This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.

* Laboratoire Matière et Systèmes Complexes (CNRS/Université Paris Diderot), in collaboration with the Laboratoire Adaptation Biologique et Vieillissement (CNRS/UPMC) and the Centre de Recherche Cardiovasculaire de Paris (Inserm/Université Paris Descartes)


More Durable Fuel Cells For Hydrogen Electric Car

Take a ride on the University of Delaware’s (UDFuel Cell bus, and you see that fuel cells can power vehicles in an eco-friendly way. In just the last two years, Toyota, BMW and Honda have released vehicles that run on fuel cells, and carmakers such as GM, BMW and VW are working on prototypes.  If their power sources lasted longer and cost less, fuel cell vehicles could go mainstream faster. Now, a team of engineers at UD has developed a technology that could make fuel cells cheaper and more durable.

Hydrogen-powered fuel cells are a green alternative to internal combustion engines because they produce power through electrochemical reactions, leaving no pollution behind. Materials called catalysts spur these electrochemical reactions. Platinum is the most common catalyst in the type of fuel cells used in vehicles. However, platinum is expensive — as anyone who’s shopped for jewelry knows. The metal costs around $30,000 per kilogram. Instead, the UD team made a catalyst of tungsten carbide, which goes for around $150 per kilogram. They produced tungsten carbide nanoparticles in a novel way, much smaller and more scalable than previous methods.

The material is typically made at very high temperatures, about 1,500 Celsius, and at these temperatures, it grows big and has little surface area for chemistry to take place on,” explains Vlachos, professor at the Catalysis Center for Energy Innovation (UD). “Our approach is one of the first to make nanoscale material of high surface area that can be commercially relevant for catalysis.”

The researchers made tungsten carbide nanoparticles using a series of steps including hydrothermal treatment, separation, reduction, carburization and more. The results are described in a paper published in Nature Communications.


Electric Car: More Silicon To Enhance Batteries

Silicon – the second most abundant element in the earth’s crust – shows great promise in Li-ion batteries, according to new research from the University of Eastern Finland. By replacing graphite anodes with silicon, it is possible to quadruple anode capacity.

In a climate-neutral society, renewable and emission-free sources of energy, such as wind and solar power, will become increasingly widespread. The supply of energy from these sources, however, is intermittent, and technological solutions are needed to safeguard the availability of energy also when it’s not sunny or windy. Furthermore, the transition to emission-free energy forms in transportation requires specific solutions for energy storage, and lithium-ion batteries are considered to have the best potential.

Researchers from the University of Eastern Finland introduced new technology to Li-ion batteries by replacing graphite used in anodes by silicon. The study analysed the suitability of electrochemically produced nanoporous silicon for Li-ion batteries. It is generally understood that in order for silicon to work in batteries, nanoparticles are required, and this brings its own challenges to the production, price and safety of the material. However, one of the main findings of the study was that particles sized between 10 and 20 micrometres and with the right porosity were in fact the most suitable ones to be used in batteries. The discovery is significant, as micrometre-sized particles are easier and safer to process than nanoparticles. This is also important from the viewpoint of battery material recyclability, among other things.

In our research, we were able to combine the best of nano– and micro-technologies: nano-level functionality combined with micro-level processability, and all this without compromising performance,” Researcher Timo Ikonen from the University of Eastern Finland says. “Small amounts of silicon are already used in Tesla’s batteries to increase their energy density, but it’s very challenging to further increase the amount,” he continues.

Next, researchers will combine silicon with small amounts of carbon nanotubes in order to further enhance the electrical conductivity and mechanical durability of the material.

The findings were published in Scientific Reports .


Green Solar Panels And Other Colors

Researchers from AMOLF, the University of Amsterdam (UvA) and the Energy Research Centre of the Netherlands (ECN) have developed a technology to create efficient bright green colored solar panels. Arrays of silicon nanoparticles integrated in the front module glass of a silicon heterojunction solar cell scatter a narrow band of the solar spectrum and create a green appearance for a wide range of angles. The remainder of the solar spectrum is efficiently coupled into the solar cell. The current generated by the solar panel is only  reduced by 10%. The realization of efficient colorful solar panels is an important step for the integration of solar panels into the built environment and landscape.
research has much focused on maximizing the electricity yield obtained from solar panels: nowadays, commercial panels have a maximum conversion efficiency from sunlight into electricity of around 22%. To reach such high efficiency, silicon solar cells have been equipped with a textured surface with an antireflection layer to absorb as much light as possible. This creates a dark blue or black appearance of the solar panels.

To create the colored solar panels the researchers have used the effect of Mie scattering, the resonant backscattering of light with a particular color by nanoparticles. They integrated dense arrays of silicon nanocylinders with a diameter of 100 nm in the top module cover slide of a high-efficiency silicon heterojunction solar cell. Due to the resonant nature of the light scattering effect, only the green part of the spectrum is reflected; the other colors are fully coupled into the solar cell. The current generated by the mini solar panel (0,7 x 0,7 cm2)  is only reduced by 10%. The solar panel appears green over a broad range of angles up to 75 degrees. The nanoparticles are fabricated using soft-imprint lithography, a technique that can readily be scaled up to large-area fabrication.
The light scattering effect due to Mie resonances is easily controllable: by changing the size of the nanoparticles the wavelength of the resonant light scattering can be tuned. Following this principle the researchers are now working to realize solar cells in other colors, and on a combination of different colors to create solar panels with a white appearance. For the large-scale application of solar panels, it is essential that their color can be tailored.

The new design was published online in the journal Applied Physics Letters.


How To Boost Body’s Cancer Defenses

After radiation treatment, dying cancer cells spit out mutated proteins into the body. Scientists now know that immune system can detect these proteins and kill cancer in other parts of the body using these protein markers as a guide – a phenomenon that University of North Carolina Lineberger Comprehensive Cancer Center (UNC Lineberg) scientists are looking to harness to improve cancer treatment.

In the journal Nature Nanotechnology, the researchers report on strides made in the development of a strategy to improve the immune system’s detection of cancer proteins by using “stickynanoparticles called “antigen-capturing nanoparticles.” They believe these particles could work synergistically with immunotherapy drugs designed to boost the immune system’s response to cancer.

Our hypothesis was that if we use a nanoparticle to grab onto these cancer proteins, we’d probably get a more robust immune response to the cancer,” said the study’s senior author Andrew Z. Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology. “We think it works because nanoparticles are attractive to the immune system. Immune cells don’t like anything that’s nano-sized; they think they are viruses, and will respond to them.”

Radiation therapy is commonly used to treat a wide array of cancers. Previously, doctors have observed a phenomenon they call the “abscopal effect,” in which a patient experiences tumor shrinkage outside of the primary site that was treated with radiation. This observation in a single patient with melanoma was reported in the New England Journal of Medicine in 2012.

Scientists believe this occurs because, after radiation, immune cells are recruited to the tumor site. Once they’ve arrived, these immune cells use mutated proteins released by dying cancer cells to train other immune cells to recognize and fight cancer elsewhere. This effect works synergistically with immunotherapy drugs called “checkpoint inhibitors,” which release the immune system’s brakes, thereby helping the body’s own defense system to attack the cancer.

Cancer cells discharge these mutated proteins – which become markers for the immune system — as a result of genetic mutations, said study co-author Jonathan Serody, MD, UNC Lineberger’s associate director for translational research.

The theory is that in cancer, tumors accumulate large numbers of mutations across their genomes, and those mutated genes can make mutant proteins, and any of those mutant proteins can be chopped up and presented to the immune system as a foreign,” said Serody, who is also the Elizabeth Thomas Professor in the UNC School of Medicine. “Your body is designed not to respond to its own proteins, but there’s no system that controls its response to new proteins, and you have a broad array of immune cells that could launch a response to them.

The UNC Lineberger researchers demonstrated in preclinical studies they could successfully design nanoparticles to capture mutated proteins released by tumors. Once these nanoparticles are taken up by immune cells, the tumor proteins attached to their surface can help immune cells recognize identify cancer cells across body.