Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year.
Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology.
Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.
Dengue virus (DENV) is transmitted by mosquitoes and is endemic in over 120 countries, causing over 350 million infections yearly. Most infections are clinically unapparent, but under specific conditions, dengue can cause severe and lethal disease. DENV has 4 distinct serotypes and secondary DENV infections are associated with hemorrhagic fever and dengue shock syndrome. This enhancement of infection complicates vaccine development and makes it necessary to induce protective immunity against all 4 serotypes. Since whole virus vaccine candidates struggle to induce protective immunity, we are developing a nanoparticle display vaccine approach. We have expressed, purified and characterized a soluble recombinant E-protein (sRecE). Regardless of nanoparticle shape or size, particulation of sRecE enhances DENV specific IgG titers and induces a robust, long lasting neutralizing antibody response and by adsorbing sRecE to the nanoparticles, we prolong the exposure of sRecE to the immune system.
Nanoparticle display shows great promise in dengue vaccine development and possibly other mosquito-borne viruses like zika virus.
A coating that blocks 90 per cent of the heat from sunlight could be used to develop smart windows
By fine-tuning the chemical composition of nanoparticles, A*STAR researchers have developed a coating that is promising for fabricating smart windows suitable for tropical countries. Such windows block almost all the infrared heat from sun rays, while admitting most of the visible light.
The transparency of glass to visible light makes it the most common way to let light into a building. But because glass is also transparent to near-infrared radiation — windows also let in heat, giving rise to the well-known greenhouse effect. While this heating is welcomed in colder climates, it means that air conditioning has to work harder to maintain a comfortable temperature in tropical climes.
Developing smart windows that allow most of the sun’s light in, while blocking near-infrared radiation, would cut energy costs and reduce carbon emissions.
“In tropical Singapore, where air conditioning is the largest component of a building’s energy requirements, even a small reduction in heat intake can translate into significant savings,” notes Hui Huang of the A*STAR Singapore Institute of Manufacturing and Technology.
Huang and his co-workers have developed such windows by coating glass with tin oxide nanoparticles doped with small amounts of the element antimony. By varying the nanoparticles’ antimony concentration, they could optimize their ability to absorb near-infrared radiation.
“Our infrared shielding coating, with 10-nanometer antimony-doped tin oxide nanoparticles, blocks more than 90 per cent of near-infrared radiation, while transmitting more than 80 per cent of visible light,” says Huang. “These figures are much better than those of coatings obtained using commercial antimony-doped tin oxide nanopowders. In particular, the infrared shielding performance of our small antimony-doped tin oxide nanocrystals is twice that of larger commercial antimony-doped tin oxide powders.”
The team produced the tiny nanoparticles using a synthesis technique known as the solvothermal method, in which precursors are heated under pressure in a special vessel, called an autoclave. The solvothermal method permits synthesis at relatively low temperatures. It also enables the nanoparticle size to be tightly controlled, which is important when trying to block some wavelengths of light while allowing others to pass through.
The work has already attracted the interest of industry. “A local glass company supporting this project is interested in licensing this smart window technology with infrared shielding,” says Huang. Potentially, the coating techniques could be applied on-site to existing windows, he adds.
Learn more: Admitting visible light, rejecting infrared heat
A recent study by researchers at the Atlanta VA took them to a not-so-likely destination: local farmers markets. They went in search of fresh ginger root.
Back at the lab, the scientists turned the ginger into what they are calling GDNPs, or ginger-derived nanoparticles. The process started simply enough, with your basic kitchen blender. But then it involved super-high-speed centrifuging and ultrasonic dispersion of the ginger juice, to break it up into single pellets. (Don’t try this at home!)
The research team, led by Dr. Didier Merlin with VA and the Institute for Biomedical Sciences at Georgia State University, believes the particles may be good medicine for Crohn’s disease and ulcerative colitis, the two main forms of inflammatory bowel disease (IBD). The particles may also help fight cancer linked to colitis, the scientists believe.
They report their findings, based on experiments with cells and mice, in the September 2016 issue of Biomaterials.
Each ginger-based nanoparticle was about 230 nanometers in diameter. More than 300 of them could fit across the width of a human hair.
Efficiently targeting the colon
Each ginger-based nanoparticle was about 230 nanometers in diameter. More than 300 of them could fit across the width of a human hair.
Fed to lab mice, the particles appeared to be nontoxic and had significant therapeutic effects:
- Importantly, they efficiently targeted the colon. They were absorbed mainly by cells in the lining of the intestines, where IBD inflammation occurs.
- The particles reduced acute colitis and prevented chronic colitis and colitis-associated cancer.
- They enhanced intestinal repair. Specifically, they boosted the survival and proliferation of the cells that make up the lining of the colon. They also lowered the production of proteins that promote inflammation, and raised the levels of proteins that fight inflammation.
Part of the therapeutic effect, say the researchers, comes from the high levels of lipids—fatty molecules—in the particles, a result of the natural lipids in the ginger plant. One of the lipids is phosphatidic acid, an important building block of cell membranes.
The particles also retained key active constituents found naturally in ginger, such as 6-gingerol and 6-shogaol. Past lab studies have shown the compounds to be active against oxidation, inflammation, and cancer. They are what make standard ginger an effective remedy for nausea and other digestion problems. Traditional cultures have used ginger medicinally for centuries, and health food stores carry ginger-based supplements—such as chews, or the herb mixed with honey in a syrup—as digestive aids.
Delivering these compounds in a nanoparticle, says Merlin’s team, may be a more effective way to target colon tissue than simply providing the herb as a food or supplement.
Ginger could be cost-effective medicine source
The idea of fighting IBD with nanoparticles is not new. In recent years, Merlin’s lab and others have explored how to deliver conventional drugs via nanotechnology. Some of this research is promising. The approach may allow low doses of drugs to be delivered only where they are needed—inflamed tissue in the colon—and thus avoid unwanted systemic effects.
The advantage of ginger, say the researchers, is that it’s nontoxic, and could represent a very cost-effective source of medicine.
The group is looking at ginger, and other plants, as potential “nanofactories for the fabrication of medical nanoparticles.”
Merlin and his VA and Georgia State University coauthors elaborated on the idea in a report earlier this year titled “Plant-derived edible nanoparticles as a new therapeutic approach against diseases.” They wrote that plants are a “bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles.”
Cancer treatments based on laser irridation of tiny nanoparticles that are injected directly into the cancer tumor are working and can destroy the cancer from within.
Researchers from the Niels Bohr Institute and the Faculty of Health Sciences at the University of Copenhagen have developed a method that kills cancer cells using nanoparticles and lasers. The treatment has been tested on mice and it has been demonstrated that the cancer tumors are considerably damaged. The results are published in the scientific journal, Scientific Reports.
Traditional cancer treatments like radiation and chemotherapy have major side affects, because they not only affect the cancer tumors, but also the healthy parts of the body. A large interdisciplinary research project between physicists at the Niels Bohr Institute and doctors and human biologists at the Panum Institute and Rigshospitalet has developed a new treatment that only affects cancer tumors locally and therefore is much more gentle on the body. The project is called Laser Activated Nanoparticles for Tumor Elimination (LANTERN). The head of the project is Professor Lene Oddershede, a biophysicist and head of the research group Optical Tweezers at the Niels Bohr Institute at the University of Copenhagen in collaboration with Professor Andreas Kjær, head of the Cluster for Molecular Imaging, Panum Institute.
After experimenting with biological membranes, the researchers have now tested the method on living mice. In the experiments, the mice are given cancer tumors of laboratory cultured human cancer cells.
“The treatment involves injecting tiny nanoparticles directly into the cancer. Then you heat up the nanoparticles from outside using lasers. It is a strong interaction between the nanoparticles and the laser light, which causes the particles to heat up. What then happens is that the heated particles damage or kill the cancer cells,” explains Lene Oddershede.
Design and effect
The small nanoparticles are between 80 and 150 nanometers in diameter (a nanometer is a millionth of a millimeter). The tested particles consist of either solid gold or a shell structure consisting of a glass core with a thin shell of gold around it. Some of the experiments aimed to find out which particles are most effective in reducing tumors.
“As physicists we have great expertise in the interaction between light and nanoparticles and we can very accurately measure the temperature of the heated nanoparticles. The effectiveness depends on the right combination between the structure and material of the particles, their physical size and the wavelength of the light,” explains Lene Oddershede.
The experiments showed that the researchers got the best results with nanoparticles that were 150 nanometers in size and consisted of a core of glass coated with gold. The nanoparticles were illuminated with near-infrared laser light, which is the best at penetrating through the tissue. In contrast to conventional radiation therapy, the near-infrared laser light causes no burn damage to the tissue that it passes through. Just an hour after the treatment, they could already directly see with PET scans that the cancer cells had been killed and the effect continued for at least two days after the treatment.
“Now we have proven that the method works. In the longer term, we would like the method to work by injecting the nanoparticles into the bloodstream, where they end up in the tumors that may have metastasized. With the PET scans we can see where the tumors are and irridate them with lasers, while also effectively assessing how well the treatment has worked shortly after the irradiation. In addition, we will coat the particles with chemotherapy, which is released by the heat and which will also help kill the cancer cells,” explains Lene Oddershede.
Rapid discovery power is similar to what gene chips offer biology
The discovery power of the gene chip is coming to nanotechnology. A Northwestern University research team is developing a tool to rapidly test millions and perhaps even billions or more different nanoparticles at one time to zero in on the best particle for a specific use.
When materials are miniaturized, their properties — optical, structural, electrical, mechanical and chemical — change, offering new possibilities. But determining what nanoparticle size and composition are best for a given application, such as catalysts, biodiagnostic labels, pharmaceuticals and electronic devices, is a daunting task.
“As scientists, we’ve only just begun to investigate what materials can be made on the nanoscale,” said Northwestern’s Chad A. Mirkin, a world leader in nanotechnology research and its application, who led the study. “Screening a million potentially useful nanoparticles, for example, could take several lifetimes. Once optimized, our tool will enable researchers to pick the winner much faster than conventional methods. We have the ultimate discovery tool.”
Using a Northwestern technique that deposits materials on a surface, Mirkin and his team figured out how to make combinatorial libraries of nanoparticles in a very controlled way. (A combinatorial library is a collection of systematically varied structures encoded at specific sites on a surface.) Their study will be published June 24 by the journal Science.
The nanoparticle libraries are much like a gene chip, Mirkin says, where thousands of different spots of DNA are used to identify the presence of a disease or toxin. Thousands of reactions can be done simultaneously, providing results in just a few hours. Similarly, Mirkin and his team’s libraries will enable scientists to rapidly make and screen millions to billions of nanoparticles of different compositions and sizes for desirable physical and chemical properties.
“The ability to make libraries of nanoparticles will open a new field of nanocombinatorics, where size — on a scale that matters — and composition become tunable parameters,” Mirkin said. “This is a powerful approach to discovery science.”
Success May Promote Solar Heat Utilization Based on Plasmon Resonance of Ceramic Materials
A research team in Japan discovered through numerical calculations that nanoparticles of transition metal nitrides and carbides absorb sunlight very efficiently, and confirmed experimentally that nitride nanoparticles, when dispersed in water, quickly raise water temperature.
A research team of Satoshi Ishii, MANA scientist, and Tadaaki Nagao, group leader, Nano-System Photonics Group, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), discovered through numerical calculations that nanoparticles of transition metal nitrides and carbides absorb sunlight very efficiently, and confirmed experimentally that nitride nanoparticles, when dispersed in water, quickly raise water temperature. These nanoparticles may be applied for heating and distillation of water through efficient sunlight use.
Sunlight is one of the most promising renewable energies. The examples of sunlight use are power generation using solar cells and water heating through photothermal conversion, a process in which absorbed sunlight is converted into heat. Water and air heating accounts for 55% of household energy consumption. If sunlight can be converted into heat very efficiently, it is possible to heat water and air without using electricity, leading to reduction of carbon dioxide emissions. Absorption of sunlight using conventional solar heat collector panels and heat collector tubes results in loss of heat through conduction. For this reason, nanoparticles that can directly heat media including water when they are dispersed in the media are attracting attention.
Australian researchers at the University of Adelaide have developed a method for embedding light-emitting nanoparticles into glass without losing any of their unique properties – a major step towards ‘smart glass’ applications such as 3D display screens or remote radiation sensors.
This new “hybrid glass” successfully combines the properties of these special luminescent (or light-emitting) nanoparticles with the well-known aspects of glass, such as transparency and the ability to be processed into various shapes including very fine optical fibres.
The research, in collaboration with Macquarie University and University of Melbourne, has been published online in the journal Advanced Optical Materials.
“These novel luminescent nanoparticles, called upconversion nanoparticles, have become promising candidates for a whole variety of ultra-high tech applications such as biological sensing, biomedical imaging and 3D volumetric displays,” says lead author Dr Tim Zhao, from the University of Adelaide’s School of Physical Sciences and Institute for Photonics and Advanced Sensing (IPAS).
“Integrating these nanoparticles into glass, which is usually inert, opens up exciting possibilities for new hybrid materials and devices that can take advantage of the properties of nanoparticles in ways we haven’t been able to do before. For example, neuroscientists currently use dye injected into the brain and lasers to be able to guide a glass pipette to the site they are interested in. If fluorescent nanoparticles were embedded in the glass pipettes, the unique luminescence of the hybrid glass could act like a torch to guide the pipette directly to the individual neurons of interest.”
Although this method was developed with upconversion nanoparticles, the researchers believe their new ‘direct-doping’ approach can be generalised to other nanoparticles with interesting photonic, electronic and magnetic properties. There will be many applications – depending on the properties of the nanoparticle.
New drug-delivery approach holds potential for treating obesity
Researchers at MIT and Brigham and Women’s Hospital have developed nanoparticles that can deliver antiobesity drugs directly to fat tissue. Overweight mice treated with these nanoparticles lost 10 percent of their body weight over 25 days, without showing any negative side effects.
The drugs work by transforming white adipose tissue, which is made of fat-storing cells, into brown adipose tissue, which burns fat. The drugs also stimulate the growth of new blood vessels in fat tissue, which positively reinforces the nanoparticle targeting and aids in the white-to-brown transformation.
These drugs, which are not FDA-approved to treat obesity, are not new, but the research team developed a new way to deliver them so that they accumulate in fatty tissues, helping to avoid unwanted side effects in other parts of the body.
“The advantage here is now you have a way of targeting it to a particular area and not giving the body systemic effects. You can get the positive effects that you’d want in terms of antiobesity but not the negative ones that sometimes occur,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.
Researchers say that sharp-edged nanoparticles can block neurodegenerative proteins that impede cognitive function.
The next challenge is making nanoparticles in this shape out of nontoxic materials.
Nanoparticles have been investigated in recent years as tools for defending the brain against neurotoxic proteins that may contribute to the onset of several different neurodegenerative disorders including Alzheimer’s disease. Such proteins, in particular amyloid-beta peptides, are thought to play a role depositing fibrous plaques on the brain that damage synapses(the contact points between neurons) and lead to a decline in cognitive capabilities.
During the onset of Alzheimer’s, amyloid beta collects in the brain centers that form new memories. As the disease progresses, these toxic protein fragments block neurotransmitters from reaching receptors on neurons. The promise of nanoparticles is that their capacity to mimic some biological functions as well as penetrate the blood–brain barrier will enable them to stop the growth of neuron-blocking fibrils better than drug compounds that might contain some variation of short peptides, antibodies or proteins—such as human serum albumin (HSA) protein. (There currently are no anti-Alzheimer’s drugs on the market.) Whereas such compounds have been shown to interfere with fibril formation, researchers are hoping that inorganic nanoparticles can do so more effectively.
Although the nanotech approach has great potential, the challenges are many, including finding a nanoparticle material that is effective yet also biocompatible and nontoxic. Another source of controversy: some nanoparticles that have been studied, including quantum dots and carbon nanotubes, seem to actually promote or accelerate fibrillation rather than prevent it.
A multidisciplinary team of researchers from the University of Michigan at Ann Arbor(U.M.) and South Korea’s Kyungpook National University claim to have resolved at least some of nanotech’s shortcomings in tackling amyloid-beta peptides. In a study published online last month in Angewandte Chemie International Edition the researchers describe inhibiting amyloid-beta fibrillation using cadmium telluride (CdTe) nanoparticles with a tetrahedral shape and negative charge.
“We decided to look at how inorganic materials can affect fibrillation of amyloid peptides, which are small proteinlike structures that form extended assemblies that look like nanofibers,” says Nicholas Kotov, a U.M. chemical engineering professor who led the study.
Whereas as these CdTe nanoparticles are not biocompatible and would be toxic in the body, the researchers chose them because they resemble in size, charge and behavior some of the proteins that have proved effective in blocking fibrillation.