Tag Archives: nanoparticle

How To Uncloak Cancer Cells And Reveal Them To The Immune System

Scientists at Johns Hopkins report they have designed and successfully tested an experimental, super small package able to deliver molecular signals that tag implanted human cancer cells in mice and make them visible for destruction by the animals’ immune systems. The new method was developed, say the researchers, to deliver an immune system “uncloaking” device directly to cancer cells.

Conventional immune therapies generally focus on manipulating patients’ immune system cells to boost their cancer-killing properties or injecting drugs that do the same but often have toxic side effectsA hallmark of cancer biology is a tumor cell’s ability to essentially hide from the immune system cells whose job is to identify and destroy cancer cells. Current cellular immunotherapies, notably CAR-T, require scientists to chemically alter and enhance a patient’s own harvested immune system T-cells — an expensive and time-consuming process, say the researchers. Other weapons in the arsenal of immunotherapies are drugs, including so-called checkpoint inhibitors, which have broad effects and often lead to unwanted immune-system-associated side effects, including damage to normal tissue.

By contrast, the Johns Hopkins team sought an immune system therapy that can work like a drug but that also individually engineers a tumor and its surrounding environment to draw the immune system cells to it, says Jordan Green, Ph.D, professor of biomedical engineering at the Johns Hopkins University School of Medicine.

A microscopic image of the nanoparticles used in the study. The black scale bar is 100 nm in size
 And our process happens entirely within the body,” Green says, “requiring no external manipulation of a patient’s cells.

To develop the new system, Green and his team, including Stephany Tzeng, Ph.D., a research associate in the Department of Biomedical Engineering at Johns Hopkins, took advantage of a cancer cell’s tendency to internalize molecules from its surroundings. “Cancer cells may be easier to directly genetically manipulate because their DNA has gone haywire, they divide rapidly, and they don’t have the typical checks and balances of normal cells,” says Green.

The team created a polymer-based nanoparticle — a tiny case that slips inside cells. They guided the nanoparticles to cancer cells by injecting them directly into the animals’ tumors. “The nanoparticle method we developed is widely applicable to many solid tumors despite their variability on an individual and tumor type level,” says Green, also a member of the Johns Hopkins Kimmel Cancer Center. Once inside the cell, the water-soluble nanoparticle slowly degrades over a day. It contains a ring of DNA, called a plasmid, that does not integrate into the genome and is eventually degraded as the cancer cell divides, but it stays active long enough to alter protein production in the cell.

The additional genomic material from the plasmid makes the tumor cells produce surface proteins called 4-1BBL, which work like red flags to say, “I’m a cancer cell, activate defenses.” The plasmid also forces the cancer cells to secrete chemicals called interleukins into the space around the cells. The 4-1BBL tags and interleukins are like magnets to immune system cells, and they seek to kill the foreign-looking cancer cells.

Results of the proof-of-concept experiments were published online in the Proceedings of the National Academy of Sciences.

Source: https://www.hopkinsmedicine.org/

Nanotherapy Reduces Plaque Buildup

A drug-coated nanoparticle reduces plaque buildup in mouse arteries without causing harmful side effects, researchers have found.

Atherosclerosis, the accumulation of plaque inside artery walls, can lead to heart attacks and strokes. It’s the world’s No. 1 killer. Available therapies treat risk factors such as high blood pressure and high cholesterol but fail to address the accumulation of diseased cells and inflammation within artery walls.

This is precision medicine,” said Nicholas Leeper, MD, professor of vascular surgery and cardiovascular medicine. “We used the nanotubes to deliver a payload like a Trojan horse.”

Leeper, who sees patients at Stanford Health Care’s vascular and endovascular care clinic, is a senior author of a paper about the research that was published Jan. 27 in Nature Nanotechnology. The other senior author is Bryan Smith, PhD, a former visiting associate professor at the School of Medicine. He is now an associate professor of biomedical engineering at Michigan State University.

Source: http://med.stanford.edu/

Copper-based Nanomaterials Kill Cancer Cells

An interdisciplinary team of scientists from KU Leuven (Belgium), the University of Bremen (Germany), the Leibniz Institute of Materials Engineering (Germany), and the University of Ioannina (Greece) has succeeded in killing tumour cells in mice using nano-sized copper compounds together with immunotherapy. After the therapy, the cancer did not return.

Recent advances in cancer therapy use one’s own immunity to fight the cancer. However, in some cases, immunotherapy has proven unsuccessful. The team of biomedical researchers, physicists, and chemical engineers found that tumours are sensitive to copper oxide nanoparticles – a compound composed of copper and oxygen. Once inside a living organism, these nanoparticles dissolve and become toxic. By creating the nanoparticles using iron oxide, the researchers were able to control this process to eliminate cancer cells, while healthy cells were not affected.

Any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart,” explain Professor Stefaan Soenen and Dr Bella B. Manshian from the Department of Imaging and Pathology, who worked together on the study. “If we would ingest metal oxides in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe, concentrations, they can actually be beneficial.

As the researchers expected, the cancer returned after treating with only the nanoparticles. Therefore, they combined the nanoparticles with immunotherapy. “We noticed that the copper compounds not only could kill the tumour cells directly, they also could assist those cells in the immune system that fight foreign substances, like tumours,” says Dr Manshian.

The combination of the nanoparticles and immunotherapy made the tumours disappear entirely and, as a result, works as a vaccine for lung and colon cancer – the two types that were investigated in the study. To confirm their finding, the researchers injected tumour cells back into the mice. These cells were immediately eliminated by the immune system, which was on the lookout for any new, similar, cells invading the body.

Source: https://nieuws.kuleuven.be/

How To Detect Blocked Arteries Effectively

Heart disease and stroke are the world’s two most deadly diseases, causing over 15 million deaths in 2016 according to the World Health Organization. A key underlying factor in both of these global health crises is the common condition, atherosclerosis, or the build-up of fatty deposits, inflammation and plaque on the walls of blood vessels. By the age of 40, around half of us will have this condition, many without symptoms.

A new nanoparticle innovation from researchers in USC Viterbi’s Department of Biomedical Engineering may allow doctors to pinpoint when plaque becomes dangerous by detecting unstable calcifications that can trigger heart attacks and strokes. The research ­­— from Ph.D. student Deborah Chin under the supervision of Eun Ji Chung, the Dr. Karl Jacob Jr. and Karl Jacob III Early-Career Chair, in collaboration with Gregory Magee, assistant professor of clinical surgery from Keck School of Medicine of USC — was recently published in the Royal Society of Chemistry’s Journal of Materials Chemistry B on 25 September 2019.

When atherosclerosis occurs in coronary arteries, blockages due to plaque or calcification-induced ruptures can lead to a clot, cutting blood flow to the heart, which is the cause of most heart attacks. When the condition occurs in the vessels leading to the brain, it can cause a stroke.

A MICROSCOPIC VIEW OF ATHEROSCLEROSIS IN A PULMONARY ARTERY

An artery doesn’t need to be 80 percent blocked to be dangerous. An artery with 45% blockage by plaques could be more rupture-prone,” Chung said. “Just because it’s a big plaque doesn’t necessarily mean it’s an unstable plaque.

Chung said that when small calcium deposits, called microcalcifications, form within arterial plaques, the plaque can become rupture prone. However, identifying whether blood vessel calcification is unstable and likely to rupture is particularly difficult using traditional CT and MRI scanning methods, or angiography, which has other risks.

Angiography requires the use of catheters that are invasive and have inherent risks of tissue damage,” said Chin, the lead author. “CT scans on the other hand, involve ionizing radiation which can cause other detrimental effects to tissue.”

Source: https://viterbischool.usc.edu/

Injection Of Nanoparticle Effective Against Melanoma

Researchers at Tel Aviv University have developed a novel nano-vaccine for melanoma, the most aggressive type of skin cancer. Their innovative approach has so far proven effective in preventing the development of melanoma in mouse models and in treating primary tumors and metastases that result from melanoma. The focus of the research is on a nanoparticle that serves as the basis for the new vaccine. The study was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology and head of the Laboratory for Cancer Research and Nanomedicine at TAU‘s Sackler Faculty of Medicine, and Prof. Helena Florindo of the University of Lisbon while on sabbatical at the Satchi-Fainaro lab at TAU. Melanoma develops in the skin cells that produce melanin or skin pigment.

The war against cancer in general, and melanoma in particular, has advanced over the years through a variety of treatment modalities, such as chemotherapy, radiation therapy and immunotherapy; but the vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” says Prof. Satchi-Fainaro. “In our study, we have shown for the first time that it is possible to produce an effective nano-vaccine against melanoma and to sensitize the immune system to immunotherapies.

The researchers harnessed tiny particles, about 170 nanometers in size, made of a biodegradable polymer. Within each particle, they “packed two peptides — short chains of amino acids, which are expressed in melanoma cells. They then injected the nanoparticles (or “nano-vaccines“) into a mouse model bearing melanoma. “The nanoparticles acted just like known vaccines for viral-borne diseases,” Prof. Satchi-Fainaro explains. “They stimulated the immune system of the mice, and the immune cells learned to identify and attack cells containing the two peptides — that is, the melanoma cells. This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

The results were published recently in Nature Nanotechnology.

Source: https://english.tau.ac.il/

Nanomachines To Deliver Cancer Drugs to Hard-to-reach Areas

In a recent study in mice, researchers found a way to deliver specific drugs to parts of the body that are exceptionally difficult to access. Their Y-shaped block catiomer (YBC) binds with certain therapeutic materials forming a package 18 nanometers wide. The package is less than one-fifth the size of those produced in previous studies, so can pass through much smaller gaps. This allows YBCs to slip through tight barriers in cancers of the brain or pancreas.

The fight against cancer is fought on many fronts. One promising field is gene therapy, which targets genetic causes of diseases to reduce their effect. The idea is to inject a nucleic acid-based drug into the bloodstream — typically small interfering RNA (siRNA) — which binds to a specific problem-causing gene and deactivates it. However, siRNA is very fragile and needs to be protected within a nanoparticle or it breaks down before reaching its target.

siRNA can switch off specific gene expressions that may cause harm. They are the next generation of biopharmaceuticals that could treat various intractable diseases, including cancer,” explained Associate Professor Kanjiro Miyata of the University of Tokyo, who jointly supervised the study. “However, siRNA is easily eliminated from the body by enzymatic degradation or excretion. Clearly a new delivery method was called for.”

Presently, nanoparticles are about 100 nanometers wide, one-thousandth the thickness of paper. This is small enough to grant them access to the liver through the leaky blood vessel wall. However some cancers are harder to reach. Pancreatic cancer is surrounded by fibrous tissues and cancers in the brain by tightly connected vascular cells. In both cases the gaps available are much smaller than 100 nanometers. Miyata and colleagues created an siRNA carrier small enough to slip through these gaps in the tissues.

We used polymers to fabricate a small and stable nanomachine for the delivery of siRNA drugs to cancer tissues with a tight access barrier,” said Miyata. “The shape and length of component polymers is precisely adjusted to bind to specific siRNAs, so it is configurable.”

Source: https://www.u-tokyo.ac.jp/

Nanoparticle Targets Tumor-infiltrating Immune Cells, Flips Switch Telling Them To Fight

Immunotherapy’s promise in the fight against cancer drew international attention after two scientists won a Nobel Prize this year for unleashing the ability of the immune system to eliminate tumor cells.

But their approach, which keeps cancer cells from shutting off the immune system’s powerful T-cells before they can fight tumors, is just one way to use the body’s natural defenses against deadly disease. A team of Vanderbilt University bioengineers today announced a major breakthrough in another: penetrating tumor-infiltrating immune cells and flipping on a switch that tells them to start fighting. The team designed a nanoscale particle to do that and found early success using it on human melanoma tissue.

Tumors are pretty conniving and have evolved many ways to evade detection from our immune system,” said John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells. “Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies. We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer.

That molecule is called cGAMP, and it’s the primary way to switch on what’s known as the stimulator of interferon genes (STING) pathway: a natural mechanism the body uses to mount an immune response that can fight viruses or bacteria or clear out malignant cells. Wilson said his team’s nanoparticle delivers cGAMP in a way that jump-starts the immune response inside the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.

While the Vanderbilt team’s research focused on melanoma, their work also indicates that this could impact treatment of many cancers, Wilson said, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.

The findings are reported in the journal Nature Nanotechnology.

Source: https://news.vanderbilt.edu/

Better Treat Salmonella Than Face Cancer

An interdisciplinary team of three Virginia Tech faculty members affiliated with the Macromolecules Innovation Institute has created a drug delivery system that could radically expand cancer treatment options. The conventional cancer treatment method of injecting nanoparticle drugs into the bloodstream results in low efficacy. Due to the complexities of the human body, very few of those nanoparticles actually reach the cancer site, and once there, there’s limited delivery across the cancer tissue.

The new system created at Virginia Tech is known as Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS). Researchers have developed a process to chemically attach nanoparticles of anti-cancer drugs onto attenuated bacteria cells, which they have shown to be more effective than the passive delivery of injections at reaching cancer sites.

NanoBEADS has produced results in both in vitro (in tumor spheroids) and in vivo (in living mice) models showing up to 100-fold improvements in the distribution and retention of nanoparticles in cancerous tissues.This is a product of Bahareh Behkam, associate professor of mechanical engineering. Collaborators on this interdisciplinary team are Rick Davis, professor of chemical engineering, and Coy Allen, assistant professor of biomedical sciences and pathobiology in the Virginia-Maryland College of Veterinary Medicine.

You can make the most amazing drugs, but if you cannot deliver it where it needs to go, it cannot be very effective,” Behkam said. “By improving the delivery, you can enhance efficacy.

Humans have noticed, even as far back as Ancient Egypt, that cancer went into remission if the patient also contracted an infection like salmonella. Neither are ideal, but humans can treat salmonella infections more effectively than cancer.

In modern times, Allen said the idea of treating cancer with infections traces back to the late 1800s and has evolved into immunotherapy, in which doctors try to activate the immune system to attack cancerous cells. Of course, salmonella is harmful to humans, but a weakened version could in theory provide the benefits of immunotherapy without the harmful effects of salmonella infection. The concept is similar to humans receiving a weakened flu virus in a vaccine to build immunity.

The work, which combines expertise in mechanical engineering, biomedical engineering, chemical engineering, and veterinary medicine, was recently detailed in Advanced Science.

Source: https://vtnews.vt.edu/

How To Manipulate And Move Cells With Light

Wits physicists demonstrate a new device for manipulating and moving tiny objects with light. When you shine a beam of light on your hand, you don’t feel much, except for a little bit of heat generated by the beam. When you shine that same light into a world that is measured on the nano– or micro scale, the light becomes a powerful manipulating tool that you can use to move objects around – trapped securely in the light.

Researchers from the Structured Light group from the School of Physics at the University of the Witwatersrand in Johannesburg, South Africa, have found a way to use the full beam of a laser light, to control and manipulate minute objects such as single cells in a human body, tiny particles in small volume chemistry, or working on future on-chip devices. While the specific technique, called holographic optical trapping and tweezing, is not new, the Wits Researchers found a way to optimally use the full force of the light – including vector light that was previously unavailable for this application. This forms the first vector holographic trap.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

Previously holographic traps were limited to particular classes of light (scalar light), so it is very exciting that we can reveal a holistic device that covers all classes of light, including replicating all previous trapping devices,” explains Professor Andrew Forbes, team leader of the collaboration and Distinguished Professor in the School of Physics where he heads up the Wits Structured Light Laboratory.

What we have done is that we have demonstrated the first vector holographic optical trapping and tweezing system. The device allows micrometer sized particles, such as biological cells, to be captured and manipulated only with light.”

Source: https://www.wits.ac.za/