How To Prevent Metastasis In Pancreatic Cancer

UCLA scientists have unlocked an important mechanism that allows chemotherapy-carrying nanoparticles—extremely small objects between 1 and 100 nanometers (a billionth of a meter)—to directly access pancreatic cancer tumors, thereby improving the ability to kill cancer cells and hence leading to more effective treatment outcome of the disease. The researchers also confirmed the key role of a peptide (an extremely small protein) in regulating vascular access of the nanoparticle to the cancer site.

The discovery is the result of a two-year study co-led by Drs. Huan Meng and André Nel, members of UCLA‘s Jonsson Comprehensive Cancer Center and the UCLA California NanoSystems Institute. The findings are important as they demonstrate how the delivery of chemotherapy to pancreatic cancer can be improved significantly through the use of smart-designed nanoparticle features.

Pancreatic ductal adenocarcinoma is generally a fatal disease, with a five-year survival rate of less than 6 percent. The introduction of nanocarriers as delivery vehicles for common chemotherapy agents such as the drug irinotecan, has led to improved survival of patients with this disease. However, the reality is that nanocarriers may not always reach their intended target in sufficient numbers because of a constraint on their ability to transit through the blood vessel wall at the tumor site, leading the encapsulated drugs to be diverted or lost before they can deliver their payload.

silica nanoparticle

A key challenge for scientists is how to help nanoparticles travel to and be retained at tumor sites. This can be accomplished by custom-designed or engineered nanoparticles that overcome common challenges, such as the presence of a dense tissue surrounding the pancreas cancer cells. Prior research has identified a major vascular access mechanism that relies on a vesicle transport system, which can be turned with a peptide called iRGD in the blood vessel wall. iRGD is therefore potentially useful to optimize the delivery of cancer drugs by the nanoparticle to the tumor.

The UCLA research team designed a nanoparticle comprised of a hollow silica core surrounded by a lipid bilayer to enhance the delivery of irinotecan in an animal model with pancreatic cancer. The invention is called a silicasome. The researchers proposed that the therapeutic benefit of the irinotecan containing nanoparticles may be enhanced when combined with the injection of iRGD. The investigators used the nanoparticle plus the iRGD to deliver irinotecan in a robust animal model for pancreatic cancer that closely mimics human disease.

The study is published online in the Journal of Clinical Investigation.

Source: http://www.cancer.ucla.edu/

How To Fast Manufacture NanoRobots

A team of researchers led by Biomedical Engineering Professor Sam Sia at Columbia Engineering has developed a way to manufacture microscale machines from biomaterials that can safely be implanted in the body. Working with hydrogels, which are biocompatible materials that engineers have been studying for decades, Sia has invented a new technique that stacks the soft material in layers to make devices that have three-dimensional, freely moving parts. The study, published online January 4, 2017, in Science Robotics, demonstrates a fast manufacturing method Sia calls “implantable microelectromechanical systems” (iMEMS).

By exploiting the unique mechanical properties of hydrogels, the researchers developed a “locking mechanism” for precise actuation and movement of freely moving parts, which can function as valves, manifolds, rotors, pumps, and drug delivery systems. They were able to tune the biomaterials within a wide range of mechanical and diffusive properties and to control them after implantation without a sustained power supply, such as a toxic battery. They then tested the payload delivery in a bone cancer model and found that the triggering of releases of doxorubicin from the device over 10 days showed high treatment efficacy and low toxicity, at 1/10th of the standard systemic chemotherapy dose.

implantable nanorobot

Overall, our iMEMS platform enables development of biocompatible implantable microdevices with a wide range of intricate moving components that can be wirelessly controlled on demand and solves issues of device powering and biocompatibility,” says Sia, also a member of the Data Science Institute. “We’re really excited about this because we’ve been able to connect the world of biomaterials with that of complex, elaborate medical devices.  Our platform has a large number of potential applications, including the drug delivery system demonstrated in our paper which is linked to providing tailored drug doses for precision medicine.”

Source: http://engineering.columbia.edu/

Gold Nanoparticles Fight Pancreatic Cancer

A diagnosis of pancreatic cancer is often a death sentence because chemotherapy and radiation have little impact on the disease. In the U.S. this year, some 53,000 new cases will be diagnosed, and 42,000 patients will die of the disease, according to the National Institute of Health. But research now being reported in ACS Nano could eventually lead to a new type of treatment based on gold nanoparticles.

pancreas2Pancreatic cancer is an aggressive, often fatal condition, but researchers are looking to gold nanoparticles to develop new treatments

Scientists from the University of Oklahoma Health Sciences Center (OUHCS) have previously studied these tiny gold particles as a vehicle to carry chemotherapy drug molecules into tumors or as a target to enhance the impact of radiation on tumors. In addition, Priyabrata Mukherjee and colleagues previously found that gold nanoparticles themselves could limit tumor growth and metastasis in a model of ovarian cancer in mice.

Now, the team has determined that the same holds true for mouse models of pancreatic cancer. But interestingly, the new work revealed details about cellular communication in the area surrounding pancreatic tumors. By interrupting this communication — which is partly responsible for this cancer’s lethal nature — the particles reduced the cell proliferation and migration that ordinarily occurs near these tumors. Gold nanoparticles of the size used in the new study are not toxic to normal cells, the researchers note.

Source: https://www.acs.org/

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/

Smart Nanoparticles Fight Multidrug-resistant Cancer

Multidrug resistance (MDR) is the mechanism by which many cancers develop resistance to chemotherapy drugs, resulting in minimal cell death and the expansion of drug-resistant tumors. To address the problem of resistance, researchers have developed nanoparticles that simultaneously deliver chemotherapy drugs to tumors and inhibit the MDR proteins that pump the therapeutic drugs out of the cell. The process is known as chemosensitization, as blocking this resistance renders the tumor highly sensitive to the cancer-killing chemotherapy.

smart nanoparticlesMDR is a major factor in the failure of many chemotherapy drugs. The problem affects the treatment of a wide range of blood cancers and solid tumors, including breast, ovarian, lung, and colon cancers. Researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a part of the National Institutes of Health (NIH), are engineering multi-component nanoparticles that significantly enhance the killing of cancer cells.
Success in this medically important endeavor has required a team with a wide range of expertise to engineer nanoparticles that survive the journey to the tumor site, enter the tumor, and successfully perform the multiple functions for chemosensitization”, says Xiaoyuan Chen, Ph.D., who is the Senior Investigator, and has lead the work. His collaborators include scientists and engineers in China at Southeast University, Shenzhen University, Guangxi Medical University, and Shanghai Jiao Tong University, in addition to chemical engineers at the University of Leeds, United Kingdom.

The results of their experiments are reported in recent articles in Scientific Reports and Applied Materials & Interfaces.

Source: https://www.nibib.nih.gov/

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.

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/

Liver Cancer: NanoDiamonds Eliminate Resistant Stem Cells

A study led by the National University of Singapore (NUS) found that attaching chemotherapy drug Epirubicin to nanodiamonds effectively eliminates chemoresistant cancer stem cells. The findings were first published online in ACS Nano, the official journal of the American Chemical Society.
liver cancer

The research team, led by Assistant Professor Edward Chow, Junior Principal Investigator at the Cancer Science Institute of Singapore (CSI Singapore) at NUS, demonstrated the use of nanotechnology to repurpose existing chemotherapy drugs as effective agents against chemoresistant cancer stem cells. Chemoresistance, which is the ability of cancer cells to escape chemotherapy treatment, is a primary cause of treatment failure in cancer. Cancer stem cells, a type of cancer cell which initiates the formation of tumours, are commonly found to be more resistant to chemotherapy than the rest of the bulk tumour, which can lead to cancer recurrence following chemotherapy treatment. As such, there is intense interest in developing new drugs or treatment strategies that overcome chemoresistance, particularly in cancer stem cells.

In this study, widely-used chemotherapy drug Epirubicin was attached to nanodiamonds, carbon structures with a diameter of about five nanometres, to develop a nanodiamond-Epirubicin drug delivery complex (EPND). The researchers found that while both standard Epirubicin as well as EPND were capable of killing normal cancer cells, only EPND was capable of killing chemoresistant cancer stem cells and preventing secondary tumour formation in xenograft models of liver cancer.

Source: http://news.nus.edu.sg/

How To Reduce Side Effects From Chemotherapy

Wichita State University (WSU) researchers are working on a new system that could decrease the negative effects of cancer drugs on patients.

WSU professors Ramazan Asmatulu, Paul Wooley and Shang-You Yang – along with several graduate students – are collaborating on research that involves the use of nanotechnology in helping patients undergoing cancer treatment.

Nanotechnology is the creation and application of nanoscale materials. One nanoparticle is about 100,000 times smaller than a strand of hair.

With that technology, the group has created nanomaterials and developed a magnetic-targeted drug delivery system with the goal of localizing as much as possible the cancer drugs to the tumor sites and therefore decreasing the negative effects of the drugs on the body. They’ve targeted their research on patients with skin and breast cancer.
chemotherapy
Skin and breast cancer patients will be exposed with the lesser amount of cancer drugs, which have too many side effects,” Asmatulu says.

So far, they have seen positive results in both “in vitro” studies (using petri dishes and test tubes) and “in vivo” studies (using mice). The group is in the final stages of receiving a patent from the study. In the future, they plan to apply the technology to humans.

Source: http://www.wichita.edu/

Tick Saliva To Combat Cancer

Brazilian doctors hope a compound found in a common blood-sucking tick can be used to break down cancerous tumours in humans after successful results in laboratory animals.
It’s not a pleasant sight; ticks having their saliva extracted. But according to researchers at the Butantan Institute in Brazil, the arachnid’s spit could be extremely valuable in fighting cancer. Project coordinator, Ana Marisa Chudzinski-Tavassi, says her team originally explored the anti blood-clotting properties of tick saliva. But they soon found that one particular molecule, Ambyomin-X, also kills malignant cells. Tests on mice and rabbits not only reduced cancerous tumours, but did so without damaging healthy cells.
tick saliva
Usually with chemotherapy, though it has a bigger effect on tumour cells than on normal cells, normal cells are also always harmed. And what we’ve seen here, even with 42 days of treatment in animals, is that we aren’t reaching normal cells. So the idea is that side effects will be far fewer“, says Doctor Ana Marisa Chudzinski-Tavassi, from the Instituto Butantan (Brazil). The tick saliva compound has successfully treated animals with cancers of the skin, pancreas, kidneys and metastases in the lungs. And Chudzinski-Tavassi says she hopes Brazil’s National Health Surveillance Agency will soon approve human clinical trials. She says these could prove an important breakthrough in the fight against cancer and put Brazil on the biotechnology map.

Source: http://www.reuters.com/
AND
http://www.butantan.gov.br/

How To Stop Pain After Cancer Chemotherapy

Karen Safranek is a survivor. Thirteen years ago, she was diagnosed with breast cancer, but after intensive chemotherapy treatment, was declared cancer free. It was good news..but while the cancer was gone, the treatment had triggered a severe case of peripheral neuropathy, a debilitating condition that causes chronic pain. “On a scale of 1 to 10 it was like a 12. It was excruciating pain. Like my feet and legs were on fire and, it’s so hard to describe, because they felt so painful and yet they were numb“says Karen. And it’s a condition that won’t go away. Dr. Charles Loprinzi of the Mayo clinic says peripheral neuropathy occurs when the brain sends pain signals to damaged nerves in a constant cycle. He says it’s a common side-effect of chemotherapy that’s difficult to treat.
neuropathy-foot-pain-
It’s a major problem from a number of chemotherapy drugs, probably the most prominent problem we have these days. For some it limits the amount of chemotherapy we can give and for some that get the chemotherapy it gets better afterwards, but for some it stays there and can be a persistent problem for years.” That was the case for Karen Safranek. For her, the pain was so severe she could barely walk. But then learned of a clinical trial at the Mayo Clinic that was testing a new device called the Scrambler, and she signed on without hesitation.. The machine, which resembles a large car battery, is designed break the pain cycle. , said DR. Charles Loprinzi, Professor of Breast Cancer research at Mayo clinic.
You put electrodes on those nerves and you give them different electrical signals and those different electrical signals kind of re-train the brain and say really this isn’t pain“, he added. After her first treatment Karen says scrambler therapy started working. After four treatments, the pain she had endured for more than a decade was gone.
It was so incredible that I hadn’t felt pain free for so many years that I guess I didn’t expect it to last. It’s working right now but I don’t know if it will be this way tomorrow.” confirms Karen Safranek.
It’s been a year since her scrambler therapy and Karen says the pain has not returned. Dr. Loprinzi says the Scrambler will not work for everyone, and that broader testing needs to be done…but eventually he says, it could be the key for many people, like Karen Safranek, to a life free of pain.
Source: http://www.ncbi.nlm.nih.gov/
AND
http://www.reuters.com/