Swiss Army Knife NanoVaccine To Fight Tumors

Scientists are using their increasing knowledge of the complex interaction between cancer and the immune system to engineer increasingly potent anti-cancer vaccines.
Now researchers at the National Institute ofBiomedical Imaging and Bioengineering (NIBIB) have developed a synergistic nanovaccine packing DNA and RNA sequences that modulate the immune response, along with anti-tumor antigens, into one smallnanoparticle. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression. Together this blocked lung tumor growth in a mouse model of metastatic colon cancer.

Large particles (left) containing the DNA and RNA components are coated with electronically charged molecules that shrink the particle. The tumor-specific neoantigen is then complexed with the surface to complete construction of the nanovaccine.
Upper left: electron micrograph of large particle

 

The molecular dance between cancer and the immune system is a complex one and scientists continue to identify the specific molecular pathways that rev up or tamp down the immune system. Biomedical engineers are using this knowledge to create nanoparticles that can carry different molecular agents that target these pathways. The goal is to simultaneously stimulate the immune system to specifically attack the tumor while also inhibiting the suppression of the immune system, which often occurs in cancer patients. The aim is to press on the gas pedal of the immune system while also releasing the emergency brake.

A key hurdle is to design a system to reproducibly and efficiently create a nanoparticle loaded with multiple agents that synergize to mount an enhanced immune attack on the tumor. Engineers at the NIBIB report the development and testing of such a nanovaccine in the journal Nature Communications.

Source: https://www.nibib.nih.gov/

New Treatment To Kill Cancer

Raise your hand if you haven’t been touched by cancer,” says Mylisa Parette to a roomful of strangers. Parette, the research manager for Keystone Nano (KN), has occasional opportunities to present her company’s technologies to business groups and wants to emphasize the scope of the problem that still confronts society. “It’s easier to see the effects of cancer when nobody raises their hand,” she says. Despite 40 years of the War on Cancer, one in two men and one in three women will be diagnosed with the disease at some point in their lifetime. Parette and her Keystone Nano colleagues are working on a new approach to cancer treatment. The company was formed from the collaboration of two Penn State faculty members who realized that the nanoparticle research that the one was undertaking could be used to solve the drug delivery problems that the other was facing.

Mark Kester, a pharmacologist at Penn State College of Medicine in Hershey, was working with a new drug that showed real promise as a cancer therapy but that could be dangerous if injected directly into the bloodstream. Jim Adair, a materials scientist in University Park, was creating nontoxic nanoparticles that could enclose drugs that might normally be toxic or hydrophobic and were small enough to be taken up by cells.

The two combined their efforts and, licensing the resulting technology from Penn State, they joined with entrepreneur Jeff Davidson, founder of the Biotechnology Institute and the Pennsylvania Biotechnology Association, to form Keystone Nano. The new company’s first hire was Parette, whose job is to translate the lab-scale technology into something that can be ramped up to an industrial scale, and to prepare that technology for FDA approval leading to clinical trials.

Davidson, Parette, and KN’s research team work out of the Zetachron building, a long, one-story science incubator a mile from Penn State’s University Park campus. Operated by the Centre County Industrial Development Corporation, the building was originally the home of the successful Penn State spin-out company that gave it its name. A second Keystone Nano lab was recently opened in the Hershey Center for Applied Research, a biotech incubator adjacent to Penn State College of Medicine.

Our excitement is that we think our technology has shown efficacy in a whole range of animal models,” Davidson, Keystone CEO, remarks during a recent meeting in the shared conference room at Zetachron. “We understand the method of action, the active ingredient. We think it has every chance of being useful in treating disease. Our question is, how do we push this forward from where we are today to determining, one way or another, that it really does work?

Keystone Nano is pioneering two approaches to cancer therapy, both of which rely on advances in nanotechnology to infiltrate tumors and deliver a therapeutic agent. The approach nearest to clinical trials is a ceramide nanoliposome, or what Davidson calls a “nano fat ball around an active ingredient.” Kester, in whose lab the approach was developed, thinks of it as a basketball with a thick bilayer coating that contains 30 percent active ceramide and a hollow interior that can hold another cancer drug.

Source: http://news.psu.edu/

How To Detect, Kill Circulating Tumor Cells

A nanolaser known as the spaser can serve as a super-bright, water-soluble, biocompatible probe capable of finding metastasized cancer cells in the blood stream and then killing these cells, according to a new research study. The spaser can be used as an optical probe and when released into the body (possibly through an injection or drinking a solution), it can find and go after circulating tumor cells (CTCs), stick to them and destroy these cells by breaking them apart to prevent cancer metastases. The spaser absorbs laser light, heats up, causes shock waves in the cell and destroys the cell membrane.

The spaser, which stands for surface plasmon amplification by stimulated emission of radiation, is a nanoparticle, about 20 nanometers in size or hundreds times smaller than human cells. It has folic acid attached to its surface, which allows selective molecular targeting of cancer cells. The folate receptor is commonly overexpressed on the surface of most human cancer cells and is weakly expressed in normal cells. The discovery was made by researchers at Georgia State University, the University of Arkansas for Medical Sciences, the University of Arkansas at Little Rock and the Siberian Branch of the Russian Academy of Science.

There is no other method to reliably detect and destroy CTCs,” said Dr. Mark Stockman, director of the Center for Nano-Optics and professor of physics at Georgia State. “This is the first. This biocompatible spaser can go after these cells and destroy them without killing or damaging healthy cells. Any other chemistry would damage and likely kill healthy cells. Our findings could play a pivotal role in providing a better, life-saving treatment option for cancer patients.”

Metastatic cancer occurs when cancer spreads to distant parts of the body, often to the bone, liver, lungs and brain, through a process called metastasis. Many types of cancers refer to this as stage IV cancer. Once cancer spreads, it can be difficult to control, and most metastatic cancer can’t be cured with current treatments, according to the National Institute of Health’s National Cancer Institute. One of the most dangerous ways metastasizing occurs is through the CTCs, which this study aims to detect and destroy using spasers. The spasers used in this study measure just 22 nanometers, setting the record for the smallest nanolasers.

The findings are published in the journal Nature Communications.

Source: http://news.gsu.edu/

Nanoparticle Shrinks Breast Tumor, Prevent Recurrence

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. A mice that received an injection with the nanoparticle showed a 70 to 80 percent reduction in tumor size. Most significantly, mice treated with these nanoparticles showed resistance to future tumor recurrence, even when exposed to cancer cells a month later.

The results show that the newly designed nanoparticle produced potent anti-tumor immune responses to HER2-positive breast cancers. Breast cancers with higher levels of HER2 protein are known to grow aggressively and spread more quickly than those without the mutation.

In this proof-of-concept study, we were astounded to find that the animals treated with these nanoparticles showed a lasting anti-cancer effect,” says Betty Y.S. Kim, M.D., Ph.D., principal investigator, and a neurosurgeon and neuroscientist who specializes in brain tumors at Mayo Clinic’s Florida campus. “Unlike existing cancer immunotherapies that target only a portion of the immune system, our custom-designed nanomaterials actively engage the entire immune system to kill cancer cells, prompting the body to create its own memory system to minimize tumor recurrence. These nanomedicines can be expanded to target different types of cancer and other human diseases, including neurovascular and neurodegenerative disorders.”

Dr. Kim’s team developed the nanoparticle, which she has named “Multivalent Bi-specific Nano-Bioconjugate Engager,” a patented technology with Mayo Clinic Ventures, a commercialization arm of Mayo Clinic.

The findings have been published in Nature Nanotechnology.

Source: https://newsnetwork.mayoclinic.org/

Nanoparticle Vaccine Against Cancer

Researchers from UT Southwestern Medical Center have developed a first-of-its-kind nanoparticle vaccine immunotherapy that targets several different cancer types.

The nanovaccine consists of tumor antigens tumor proteins that can be recognized by the immune system – inside a synthetic polymer nanoparticle. Nanoparticle vaccines deliver minuscule particulates that stimulate the immune system to mount an immune response. The goal is to help people’s own bodies fight cancer.


cancer-cells-

What is unique about our design is the simplicity of the single-polymer composition that can precisely deliver tumor antigens to immune cells while stimulating innate immunity. These actions result in safe and robust production of tumor-specific T cells that kill cancer cells,” said Dr. Jinming Gao, a Professor of Pharmacology and Otolaryngology in UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.

A study outlining this research, published online today in Nature Nanotechnology, reported that the nanovaccine had anti-tumor efficacy in multiple tumor types in mice.

The research was a collaboration between the laboratories of study senior authors Dr. Gao and Dr. Zhijian “James” Chen, Professor of Molecular Biology and Director of the Center for Inflammation Research. The Center was established in 2015 to study how the body senses infection and to develop approaches to exploit this knowledge to create new treatments for infection, immune disorders, and autoimmunity.

Source: http://www.utsouthwestern.edu/

Efficient, Fast, Large-scale 3-D Manufacturing

Washington State University (WSU) researchers have developed a unique, 3-D manufacturing method that for the first time rapidly creates and precisely controls a material’s architecture from the nanoscale to centimeters – with results that closely mimic the intricate architecture of natural materials like wood and bone.

3D manufacturing Hex-Scaffold-web-

This is a groundbreaking advance in the 3-D architecturing of materials at nano- to macroscales with applications in batteries, lightweight ultrastrong materials, catalytic converters, supercapacitors and biological scaffolds,” said Rahul Panat, associate professor in the School of Mechanical and Materials Engineering, who led the research. “This technique can fill a lot of critical gaps for the realization of these technologies.”

The WSU research team used a 3-D printing method to create foglike microdroplets that contain nanoparticles of silver and to deposit them at specific locations. As the liquid in the fog evaporated, the nanoparticles remained, creating delicate structures. The tiny structures, which look similar to Tinkertoy constructions, are porous, have an extremely large surface area and are very strong.

The researchers would like to use such nanoscale and porous metal structures for a number of industrial applications; for instance, the team is developing finely detailed, porous anodes and cathodes for batteries rather than the solid structures that are now used. This advance could transform the industry by significantly increasing battery speed and capacity and allowing the use of new and higher energy materials.

They report on their work in the journal  Science Advances  and have filed for a patent.

Source: https://news.wsu.edu/

Nanoparticles Trigger Dormant Viruses In Lung Cells

Nanoparticles from combustion engines can activate viruses that are dormant in lung tissue cells. This is the result of a study by researchers of Helmholtz Zentrum München, a partner in the German Center for Lung Research (DZL), which has now been published in the journal ‘Particle and Fibre Toxicology‘.

To evade the immune system, some viruses hide in cells of their host and persist there. In medical terminology, this state is referred to as a latent infection. If the immune system becomes weakened or if certain conditions change, the viruses become active again, begin to proliferate and destroy the host cell. A team of scientists led by Dr. Tobias Stöger of the Institute of Lung Biology and Prof. Dr. Heiko Adler, deputy head of the research unit Lung Repair and Regeneration at Helmholtz Zentrum München, now report that nanoparticles can also trigger this process.

car engine nanoparticles

From previous model studies we already knew that the inhalation of nanoparticles has an inflammatory effect and alters the immune system,” said study leader Stöger. Together with his colleagues Heiko Adler and Prof. Dr. Philippe Schmitt-Kopplin, he showed that “an exposure to nanoparticles can reactivate latent herpes viruses in the lung.

Source: https://www.helmholtz-muenchen.de/

Nanoparticles Overcome Treatment-Resistant Breast Cancer

Researchers at the University of Cincinnati (UC) College of Medicine have been able to generate multifunctional RNA nanoparticles that could overcome treatment resistance in breast cancer, potentially making existing treatments more effective in these patients. The research team  led by Xiaoting Zhang, PhD, associate professor at the UC College of Medicine, demonstrates that using a nanodelivery system to target HER2-positive breast cancer and stop production of the protein MED1 could slow tumor growth, stop cancer from spreading and sensitize the cancer cells to treatment with tamoxifen, a known therapy for estrogen-driven cancer.
nanoparticles-300x225
Most breast cancers express estrogen receptors, and the anti-estrogen drug tamoxifen has been widely used for their treatment,” says Zhang, who is also a member of the Cincinnati Cancer Center and the UC Cancer Institute. “Unfortunately, up to half of all estrogen receptor-positive tumors are either unresponsive or later develop resistance to the therapy. In this study, we have developed a highly innovative design that takes advantage of the co-overexpression of HER2 and MED1 in these tumors.”
Zhang and researchers in his lab found that these RNA nanoparticles were able to selectively bind to HER2-overexpressing breast tumors, eliminating MED1 expression and significantly decreasing estrogen receptor-controlled target gene production. The RNA nanoparticles not only reduced the growth and spread of the HER2-overexpressing breast cancer tumors, but also sensitized them to tamoxifen treatment.

The study, has been published in the online edition of ACS Nano.

Source: http://healthnews.uc.edu/

Tatoo Therapy

A temporary tattoo to help control a chronic disease might someday be possible, according to scientists at Baylor College of Medicine who tested antioxidant nanoparticles created at Rice University. A proof-of-principle study led by Baylor scientist Christine Beeton published by Nature’s online, open-access journal Scientific Reports shows that nanoparticles modified with polyethylene glycol are conveniently choosy as they are taken up by cells in the immune system. That could be a plus for patients with autoimmune diseases like multiple sclerosis, one focus of study at the Beeton lab.

tatoo-therapy

“Placed just under the skin, the carbon-based particles form a dark spot that fades over about one week as they are slowly released into the circulation,” Beeton said. T and B lymphocyte cells and macrophages are key components of the immune system. However, in many autoimmune diseases such as multiple sclerosis, T cells are the key players. One suspected cause is that T cells lose their ability to distinguish between invaders and healthy tissue and attack both.

In tests at Baylor, nanoparticles were internalized by T cells, which inhibited their function, but ignored by macrophages. “The ability to selectively inhibit one type of cell over others in the same environment may help doctors gain more control over autoimmune diseases,” Beeton said. “The majority of current treatments are general, broad-spectrum immunosuppressants,” said Redwan Huq, lead author of the study and a graduate student in the Beeton lab. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer. So we get excited when we see something new that could potentially enable selectivity.” Since the macrophages and other splenic immune cells are unaffected, most of a patient’s existing immune system remains intact, he added.

 

Source: http://news.rice.edu/

Water Repellent Spray Coating

Scientists at The Australian National University (ANU) have developed a new spray-on material with a remarkable ability to repel water. The new protective coating could eventually be used to waterproof mobile phones, prevent ice from forming on aeroplanes or protect boat hulls from corroding.

water-repellent-coating-2

The surface is a layer of nanoparticles, which water slides off as if it’s on a hot barbecue,” said PhD student William Wong, from the Nanotechnology Research Laboratory at the ANU Research School of Engineering. The team created a much more robust coating than previous materials by combining two plastics, one tough and one flexible.

It’s like two interwoven fishing nets, made of different materials,” Mr Wong said. The water-repellent or superhydrophobic coating is also transparent and extremely resistant to ultraviolet radiation. Lead researcher and head of the Nanotechnology Research Laboratory, Associate Professor Antonio Tricoli, said the new material could change how we interact with liquids“It will keep skyscraper windows clean and prevent the mirror in the bathroom from fogging up,” Associate Professor Tricoli said. “The key innovation is that this transparent coating is able to stabilise very fragile nanomaterials resulting in ultra-durable nanotextures with numerous real-world applications.”

The team developed two ways of creating the material, both of which are cheaper and easier than current manufacturing processes. One method uses a flame to generate the nanoparticle constituents of the material. For lower temperature applications, the team dissolved the two components in a sprayable form. In addition to waterproofing, the new ability to control the properties of materials could be applied to a wide range of other coatings, said Mr Wong. “A lot of the functional coatings today are very weak, but we will be able to apply the same principles to make robust coatings that are, for example, anti-corrosive, self-cleaning or oil-repellent,” he said.

The research is published in ACS Appl. Mater. Interfaces 2016, 8, 13615−13623.

Source: http://www.anu.edu.au/

Cancer: How To Shrink Tumors

Math, biology and nanotechnology are becoming strange, yet effective bed-fellows in the fight against cancer treatment resistance. Researchers at the University of Waterloo and Harvard Medical School have engineered a revolutionary new approach to cancer treatment that pits a lethal combination of drugs together into a single nanoparticle. Their work, published online on June 3, 2016 in the  journal ACS Nano, finds a new method of shrinking tumors and prevents resistance in aggressive cancers by activating two drugs within the same cell at the same time. Every year thousands of patients die from recurrent cancers that have become resistant to therapy, resulting in one of the greatest unsolved challenges in cancer treatment. By tracking the fate of individual cancer cells under pressure of chemotherapy, biologists and bioengineers at Harvard Medical School studied a network of signals and molecular pathways that allow the cells to generate resistance over the course of treatment.

anti cancer nanoparticle

Using this information, a team of applied mathematicians led by Professor Mohammad Kohandel at the University of Waterloo (Canada), developed a mathematical model that incorporated algorithms that define the phenotypic cell state transitions of cancer cells in real-time while under attack by an anticancer agent. The mathematical simulations enabled them to define the exact molecular behavior and pathway of signals, which allow cancer cells to survive treatment over time.

They discovered that the PI3K/AKT kinase, which is often over-activated in cancers, enables cells to undergo a resistance program when pressured with the cytotoxic chemotherapy known as Taxanes, which are conventionally used to treat aggressive breast cancers. This revolutionary window into the life of a cell reveals that vulnerabilities to small molecule PI3K/AKT kinase inhibitors exist, and can be targeted if they are applied in the right sequence with combinations of other drugs.

Previously theories of drug resistance have relied on the hypothesis that only certain, “privileged” cells can overcome therapy. The mathematical simulations demonstrate that, under the right conditions and signaling events, any cell can develop a resistance program.

Only recently have we begun to appreciate how important mathematics and physics are to understanding the biology and evolution of cancer,” said Professor Kohandel. “In fact, there is now increasing synergy between these disciplines, and we are beginning to appreciate how critical this information can be to create the right recipes to treat cancer.”

Source: https://uwaterloo.ca/

Nanoparticle Attacks Agressive Thyroid Cancer

Anaplastic thyroid cancer (ATC), the most aggressive form of thyroid cancer, has a mortality rate of nearly 100 percent and a median survival time of three to five months. One promising strategy for the treatment of these solid tumors and others is RNA interference (RNAi) nanotechnology, but delivering RNAi agents to the sites of tumors has proved challenging. Investigators at Brigham and Women’s Hospital, together with collaborators from Massachusetts General Hospital, have developed an innovative nanoplatform that allows them to effectively deliver RNAi agents to the sites of cancer and suppress tumor growth and reduce metastasis in preclinical models of ATC.

thyroid cancer

We call this a ‘theranostic’ platform because it brings a therapy and a diagnostic together in one functional nanoparticle,” said co-senior author Jinjun Shi, PhD, assistant professor of Anesthesia in the Anesthesia Department. “We expect this study to pave the way for the development of theranostic platforms for image-guided RNAi delivery to advanced cancers.”

RNAi, the discovery of which won the Nobel Prize in Physiology or Medicine 10 years ago, allows researchers to silence mutated genes, including those upon which cancers depend to grow and survive and metastasize. Many ATCs depend upon mutations in the commonly mutated cancer gene BRAF. By delivering RNAi agents that specifically target and silence this mutated gene, the investigators hoped to stop both the growth and the spread of ATC, which often metastasizes to the lungs and other organs.

When RNAi is delivered on its own, it is usually broken down by enzymes or filtered out by the kidneys before it reaches tumor cells. Even when RNAi agents make it as far as the tumor, they are often unable to penetrate or are rejected by the cancer cells. To overcome these barriers, the investigators used nanoparticles to deliver the RNAi molecules to ATC tumors. In addition, they coupled the nanoparticles with a near-infrared fluorescent polymer, which allowed them to see where the nanoparticles accumulated in a mouse model of ATC.

The results have appeared in the journal  Proceedings of the National Academy of Sciences.

Source: http://www.brighamandwomens.org/