How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

Artificial Skin Breathes like Human Skin

A scientist in Chile is using microscopic algae to make skingreen skin. These very small, very simple plants are being used to develop a new artificial skin for humans. The problem with most current artificial skin is that there are no blood vessels – so the man-made skin cannot produce the oxygen it needs to live. But with algae, the skin can breathe through the process of photosynthesis.

artificial-skin-breathesCLICK ON THE IMAGE TO ENJOY THE VIDEO

What we’re basically doing is incorporating micro-algae, which are like microscopic plants into different types of materials. For example, when we apply artificial skin what we have is the characteristics of plants which means when it is lit up it can produce oxygen,” says Tomas Egana from the Chile’s Catholic University, professor at the Institute of biological engineering. And the benefits of the algae could go beyond just a cosmetic improvement. It may help human skin heal itself: “These micro-algae can be genetically modified. So that in addition to producing oxygen they will produce different factors, for example antibiotics, anti-inflammatories and pro-regenerative molecules. So, we are going to have material which is completely artificial and still, which is a structure that has material that is alive.

Professor Egana says the green-colored skin could eventually be used to help patients treat open wounds, tumors and possibly avoid amputations. But patients need not worry about looking like the Incredible Hulk. Egana believes the green color will fade over time as the algae dies. At the moment, animal testing has proven a success. Human trials are expected next year.

Source: http://www.reuters.com/

Triggered Immune Cells Attack Cancer

Stanford researchers accidentally discovered that iron nanoparticles invented for anemia treatment have another use: triggering the immune system’s ability to destroy tumor cellsIron nanoparticles can activate the immune system to attack cancer cells, according to a study led by researchers at the Stanford University School of Medicine. The nanoparticles, which are commercially available as the injectable iron supplement ferumoxytol, are approved by the Food and Drug Administration (FDA) to treat iron deficiency anemia.

The mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy cancer cells, suggesting that the nanoparticles could complement existing cancer treatments.

macrophages-attack-cancerA mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy tumor cells.

It was really surprising to us that the nanoparticles activated macrophages so that they started to attack cancer cells in mice,” said Heike Daldrup-Link, MD, who is the study’s senior author and an associate professor of radiology at the School of Medicine. “We think this concept should hold in human patients, too.

The study showed that the iron nanoparticles switch the macrophages back to their cancer-attacking state, as evidenced by tracking the products of the macrophages’ metabolism and examining their patterns of gene expression.

Furthermore, in a mouse model of breast cancer, the researchers demonstrated that the ferumoxytol inhibited tumor growth when given in doses, adjusted for body weight, similar to those approved by the FDA for anemia treatment.

Daldrup-Link’s team conducted an experiment that used three groups of mice: an experimental group that got nanoparticles loaded with chemo, a control group that got nanoparticles without chemo and a control group that got neither. The researchers made the unexpected observation that the growth of the tumors in control animals that got nanoparticles only was suppressed compared with the other controls.

The discovery, described in a paper published online in Nature Nanotechnology, was made by accident while testing whether the nanoparticles could serve as Trojan horses by sneaking chemotherapy into tumors in mice.
Source: http://med.stanford.edu/

How Anthrax Toxin Kills Tumors

Over the past decades, researchers have become particularly interested in the idea of hijacking the cell-killing capacity of bacterial toxins to target tumor cells. So far, engineered toxins from Pseudomonas, anthrax toxin, and ricin showed promising results in treating tumors in mice. But the mechanism of action of these toxins remains elusive. Now a new study in the journal Proceedings of the National Academy of Science sheds light on tumor proteins used by Bacillus anthracis to kill tumors.

anthrax-tumorModified anthrax toxin specifically targets the tumor vasculature to exert anti-tumor effects

As we worked more and more on anthrax toxin, we discovered, along with others, features of it that made it attractive as another bacterial protein toxin that could be redirected for curing cancer,” said Stephen Leppla from the National Institute of Allergy and Infectious Disease, senior author of the study.

Anthrax toxin has three sub-components that assemble within host cells before exerting their toxicity. PA, the cell-binding component of anthrax toxin, interacts with two cell surface proteins: tumor endothelium-marker 8 (TEM8) and capillary morphogenesis protein-2 (CMG2).

Finding that anthrax toxin specifically acts on tumor vasculature is particularly promising, given the stability of tumor endothelial cells compared to mutation-prone stromal cells. Anthrax toxin could thus be used to treat widely different tumors. “We would like to get to phase I human trials,” said Leppla. “We have collaborators who are testing our reagents in both cats and dogs who also get cancer but don’t have good treatment options. We’re hoping that this will provide further evidence that these reagents are effective.

Source: http://www.biotechniques.com/

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/

Gentle Cancer Treatment Using Nanoparticles

Cancer treatments based on laser irradiation 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  (Denmark) 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.

mouse with cancer treatment

 
The drawing shows a mouse with a cancerous tumor on its hind leg. The nanoparticles are injected directly into the tumor, which is then flashed with near infrared laser light. Near infrared laser light penetrates through the tissue well and causes no burn damage
 

 

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. There 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.

The results are published in the scientific journal, Scientific Reports.

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/

How To Break The Brain Barrier To Kill Cancer

Using a laser probe, neurosurgeons at Washington University School of Medicine in St. Louis have opened the brain’s protective cover, enabling them to deliver chemotherapy drugs to patients with a form of deadly brain cancer. In a pilot study, 14 patients with glioblastoma – the most common and aggressive type of brain cancer – underwent minimally invasive laser surgery to treat a recurrence of their tumors. Heat from the laser is known to kill brain tumor cells but, unexpectedly, the researchers found that the technology can penetrate the blood-brain barrier.

laser breaks brain barrierCLICK ON THE IMAGE TO ENJOY THE VIDEO

The laser treatment kept the blood-brain barrier open for four to six weeks, providing us with a therapeutic window of opportunity to deliver chemotherapy drugs to the patients,” said co-corresponding author Eric C. Leuthardt, MD, a Washington University professor of neurosurgery who treats patients at Barnes-Jewish Hospital. “This is crucial because most chemotherapy drugs can’t get past the protective barrier, greatly limiting treatment options for patients with brain tumors. We are closely following patients in the trial,” said Leuthardt, who also is a Siteman Cancer Center member. “Our early results indicate that the patients are doing much better on average, in terms of survival and clinical outcomes, than what we would expect. We are encouraged but very cautious because additional patients need to be evaluated before we can draw firm conclusions.

The study is published online Feb. 24 in the journal PLOS ONE.

Source: https://medicine.wustl.edu/

New Cancer Treatment Could Eliminate Lung Metastases

A team of investigators from Houston Methodist Research Institute may have transformed the treatment of metastatic triple negative breast cancer by creating the first drug to successfully eliminate lung metastases in mice.
The majority of cancer deaths are due to metastases to the lung and liver, yet there is no cure. Existing cancer drugs provide limited benefit due to their inability to overcome biological barriers in the body and reach the cancer cells in sufficient concentrations. Houston Methodist nanotechnology and cancer researchers have solved this problem by developing a drug that generates nanoparticles inside the lung metastases in mice.
In this study, 50 percent of the mice treated with the drug had no trace of metastatic disease after eight months. That’s equivalent to about 24 years of long-term survival following metastatic disease for humans.

Due to the body’s own defense mechanisms, most cancer drugs are absorbed into healthy tissue causing negative side effects, and only a fraction of the administered drug actually reaches the tumor, making it less effective, said Mauro Ferrari, Ph.D, president and CEO of the Houston Methodist Research Institute. This new treatment strategy enables sequential passage of the biological barriers to transport the killing agent into the heart of the cancer. The active drug is only released inside the nucleus of the metastatic disease cell, avoiding the multidrug resistance mechanism of the cancer cells. This strategy effectively kills the tumor and provides significant therapeutic benefit in all mice, including long-term survival in half of the animals.

cancer treatment by injection

This may sound like science fiction, like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational. We invented a method that actually makes the nanoparticles inside the cancer and releases the drug particles at the site of the cellular nucleus. With this injectable nanoparticle generator, we were able to do what standard chemotherapy drugs, vaccines, radiation, and other nanoparticles have all failed to do,” said Ferrari.

The research has been published in Nature Biotechnology .

Source: http://houstonmethodist.org/

How To Turn Off Cancer Cells

Researchers offer proof of concept for new nanomedicine designed to inhibit tumor growth by keeping cancer dormant. A new Tel Aviv University (TAU) in Israel study offers tangible hope of a therapeutic pathway to keep osteosarcoma* lesions dormant. It also provides the fundamental basic-science for novel nanomedicines tailored to maintain cancer cells in an asymptomatic state. The proof of concept was pioneered by Prof. Ronit Satchi-Fainaro,  Head of TAU‘s Cancer Angiogenesis and Nanomedicine Laboratory.

onoffswitch

We want to keep the cancer ‘switchturned off,” said Prof. Satchi-Fainaro. “Once osteosarcoma metastasizes away from the primary tumor site, there is no effective treatment, just different ways of prolonging life“.
A 1993 article in the New England Journal of Medicine by William C. Black and H. Gilbert Welch about dormant tumor lesions discovered in the autopsies of people who were considered healthy until their accident-related deaths provided the basis for our research. We decided to investigate osteosarcoma recurrence, with an eye toward the potentially therapeutic value of dormancy.”

Osteosarcoma* tumors may return with a vengeance, even if they’re caught early and excised from a primary site. In the case of “minimal residual disease,” cancerous cells left after surgery in a localized spot suddenlyturn on,” and the disease reappears. In the other case of “dormant micrometastatic lesions,” mini-tumors undetected by current imaging technologies suddenly reemerge as large macro-metastases, primarily in the lungs.

We wanted to understand what causes the cancer cells to ‘switch on’ in these cases,” said Prof. Satchi-Fainaro. “As long as cancer cells remain asymptomatic and dormant, cancer is a manageable disease. Many people live with thyroid lesions without their knowledge, for example. Ours is a very optimistic approach, and we believe it could apply to other cancers as well.”

The study is the fruit of a five-year collaboration between Prof. Satchi-Fainaro’s team, led by TAU PhD student Galia Tiram, and the laboratories of Rainer Haag and Marcelo Calderón of Freie Universität Berlin (Germany). It was recently published in the journal ACS Nano.

Osteosarcoma is a cancer that develops in the bones of children and adolescents. It is one of the most aggressive cancers, with only a 15 per cent, five-year survival rate when diagnosed in an advanced metastatic stage. There are approximately 800 new cases diagnosed each year in the US, and no viable treatments.

Source: https://www.aftau.org/

Nanoparticles Trigger Immune System To Destroy Cancer

The shells of a common plant virus, inhaled into a lung tumor or injected into ovarian, colon or breast tumors, not only triggered the immune system in mice to wipe out the tumors, but provided systemic protection against metastases, researchers from Case Western Reserve University and Dartmouth University report. The scientists tested a 100-year-old idea called in-situ vaccination. The idea is to put something inside a tumor and disrupt the environment that suppresses the immune system, thus allowing the natural defense system to attack the malignancy.

That something—the hard coating of cowpea* mosaic virus—caused no detectible side effects, which are a common problem with traditional therapies and some immunotherapies.

cowpeas

The cowpea virus-based nanoparticles act like a switch that turns on the immune system to recognize and fight against the tumor – as well as to remember it,” said Nicole Steinmetz, an assistant professor of biomedical engineering at Case Western Reserve, appointed by the Case Western Reserve School of Medicine.

The particles are shockingly potent,” said Steven Fiering, professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine. “They’re easy to make and don’t need to carry antigens, drugs or other immunostimmulatory agents on their surface or inside.”

The team’s research is published in the journal Nature Nanotechnology.

* Cowpeas are one of the most important food legume crops in the semiarid tropics covering Asia, Africa, southern Europe, and Central and South America

Source: http://blog.case.edu/

Sunscreen Nanoparticles Eliminate Skin-Cancer

A research team including scientists funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) has developed a nanotechnology-based sunscreen that provides excellent protection from ultraviolet (UV) damage while eliminating a number of harmful effects of currently used sunscreens. The team encapsulated the UV-blocking compounds in bio-adhesive nanoparticles (BNPs), which adhere to the skin well, but do not penetrate beyond the skin’s surface. These properties resulted in highly effective UV protection in a mouse model, without the adverse effects observed with commercial sunscreens, including penetration into the bloodstream and generation of reactive oxygen species, which can damage DNA and lead to cancer. Commercial sunscreens use compounds that effectively filter out damaging UV light. However, there is concern that these agents have a variety of harmful effects due to penetration past the surface skin. For example, these products have been found in human breast tissue and urine and are known to disrupt the normal function of some hormones. Also, the exposure of the UV filters to light can produce toxic reactive oxygen species that are destructive to cells and tissues and can cause tumors through DNA damage.


sunscreen

 

BNPs remain on skin for a full day but are gone due to normal exfoliation in five days

This work applies a novel bioengineering idea to a little known but significant health problem, adds Jessica Tucker, Ph.D., Director of the NIBIB Program in Delivery Systems and Devices for Drugs and Biologics. “While we are all familiar with the benefits of sunscreen, the potential toxicities from sunscreen due to penetration into the body and creation of DNA-damaging agents are not well known.Bioengineering sunscreen to inhibit penetration and keep any DNA-damaging compounds isolated in the nanoparticle and away from the skin is a great example of how a sophisticated technology can be used to solve a problem affecting the health of millions of people.

Bioengineers and dermatologists at Yale University in New Haven, Connecticut combined their expertise in nanoparticle-based drug delivery and the molecular and cellular characteristics of the skin to address these potential health hazards of current commercial sunscreens. The results of their collaboration were reported in the September issue of Nature Materials.

Source: http://www.nibib.nih.gov/