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/

“Liquid Biopsy” Chip Detects Metastatic Cancer Cells in a Drop of Blood

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices.

liquid-biopsy-chip-test

The chip is tested in the lab. The electrodes detect electrical changes that occur when cancer cells are captured (click on the image to enjoy the video)

The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,”  could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.

Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds.

The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.

The findings have been described in  the journal Nanotechnology,

Source: https://www.wpi.edu/

How To Stop The Spread Of Breast Cancer

A breakthrough technology that harnesses manmade nanoparticles could one day become an important new weapon in the fight against cancer. The technique, which appeared to successfully stop the spread of breast cancer in mice, was unveiled by scientists from the Cold Spring Harbor Laboratory, Dana-Farber Cancer Institute, Stony Brook University, and a host of other research institutions in the journal Science Translational Medicine.

Next-generation cancer fighting therapies on the market today use the body’s immune system to combat tumors, as does experimental technology like CRISPR gene-editing. But the new nanotech has a different target: The cells that actually help cancer metastasize and spread throughout the body. These immune cells, which are meant to ward off infections, create structures called neutrophil extracellular traps (NETs) that help them fight bacteria. But NETs can actually wind up helping spread the cancer by creating tissue openings that cancerous cells can exploit, study co-author Mikala Egeblad explained.

 breast-cancer-cells

A high magnification of an intact neutrophil (yellow arrow) and a NET (white arrow)

So the researchers created a new particle coated with a special enzyme that can kill these cells before the cancer can use them to metastasize. The results were modest, but promising: Three out of the nine mice given the nanoparticle showed no evidence of breast cancer progression, while all mice in the control group continued to worsen.

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/

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/

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/

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/

How To Inhibit Breast Cancer Metastasis

Researchers at Case Western Reserve University combined finely crafted nanoparticles with one of nature’s potent disrupters to prevent the spread of triple-negative breast cancer in mouse models. The highly aggressive cancer subtype is difficult to manage and, currently, the FDA has no approved targeted treatments. But striking results from a new study, published in the journal Cancer Research make the researchers optimistic they have a potential game-changer for triple negative cancer and more.


breast cancer

There are multiple targets within a cell,” said William Schiemann, professor of oncology at the Case Western Reserve School of Medicine and the Case Comprehensive Cancer Center, and a leader of the research. “With this technology, we can target any gene or any location, for other cancers, more diseases—potentially even immunology-based diseases.”

Regular injections of nanoparticles carrying siRNA,  silenced the gene that regulates expression of the protein β3 integrin. Expression of β3 integrin in the cell-development process called the endothelial-mesenchymal transition (EMT), is essential for the cancer to spread from its primary tumor.

Nearly 15 percent of breast cancers in the United States are triple negative, and the subtype is most prevalent among African-American women in their 20s and 30s. According to the National Cancer Institute, the five-year survival rate for women whose cancer is discovered early and contained to a primary tumor is 98 percent. But, the survival rate for those diagnosed with distant metastases plummets to less than 25 percent.

To try to tackle metastasis, Schiemann teamed with Zheng-Rong Lu, the M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve, Jenny Parvani, now a postdoctoral investigator, PhD student Maneesh Gujrati and undergraduate student Margaret Mack. Lu’s lab has been developing lipid-based nanoparticles to deliver medicines to specific targets in the body for a decade. Lipids include fats and oils, but these organic molecules are also building blocks in cell structures and functions.

In this study, five mice with a mouse version of triple-negative breast cancer were injected with particles every five days for 14 weeks. Compared to control mice, the treated mice’s tumors shrunk significantly, but more importantly, the treatment significantly inhibited metastasisFour weeks after treatment was stopped, the treated mice remained tumor free while cancer continued to grow in untreated controls. No significant difference in body weight across treatment groups and controls were found, indicating low toxicity of the treatments.

Source: http://blog.case.edu/

Graphene Attacks Cancer Stem Cells

University of Manchester scientists have used graphene to target and neutralisecancer stem cells while not harming other cells. Writing in the journal Oncotarget, the team of researchers led by Professor Michael Lisanti and Dr Aravind Vijayaraghavan has shown that graphene oxide , a modified form of graphene, acts as an anti-cancer agent that selectively targets cancer stem cells (CSCs).
In combination with existing treatments, this could eventually lead to tumour shrinkage as well as preventing the spread of cancer and its recurrence after treatment. However, more pre-clinical studies and extensive clinical trials will be necessary to move this forward into the clinic to ensure patient benefit.

graphene interacts with cellGraphene oxide flakes interacting with cell membranes

Cancer stem cells possess the ability to give rise to many different tumour cell types. They are responsible for the spread of cancer within the body – known as metastasis– which is responsible for 90% of cancer deaths“, explains Professor Lisanti, the Director of the Manchester Centre for Cellular Metabolism within the University’s Institute of Cancer Sciences.
They also play a crucial role in the recurrence of tumours after treatment. This is because conventional radiation and chemotherapies only kill the ‘bulk’ cancer cells, but do not generally affect the CSCs.”

Source: http://www.manchester.ac.uk/

Cancer Cells Love Soft Beds

 Cancer cells that break away from tumors to go looking for a new home may prefer to settle into a soft bed, according to new findings from researchers at the University of Illinois.
Some particularly enterprising cancer cells can cause a cancer to spread to other organs, called metastasis, or evade treatment to resurface after a patient is thought to be in remission. The Illinois team, along with colleagues in China, found that these so-called tumor-repopulating cells may lurk quietly in stiffer cellular environments, but thrive in a softer space.

metastasis2

What causes relapse is not clear,” said study leader Ning Wang. Wang is the Leonard C. and Mary Lou Hoeft Professor in Engineering and professor of mechanical science and engineering of the U. of I. “Why are there a few cells left that can come back stronger? We thought cancer cells may have some properties in common with stem cells, which allows them to metastasize to different tissues. Normally, if you take a liver cell and put it in your lung, it will die. But an undifferentiated cell will live.

The results appear in the journal Nature Communications.

Source: http://news.illinois.edu/

Simple Breathalyzer To Detect Lung Cancer

Researchers from Tel Aviv University and partner institutions develop device that spots lung cancer to stop it in its tracks. Lung cancer causes MORE deaths in the U.S. than the next three most common cancers combined (colon, breast, and pancreatic). The reason for the striking mortality rate is simple: poor detection. Lung cancer attacks without leaving any fingerprints, quietly afflicting its victims and metastasizing uncontrollably — to the point of no return. Now a new device developed by a team of Israeli, American, and British cancer researchers may turn the tide by both accurately detecting lung cancer and identifying its stage of progression. The breathalyzer test, embedded with a “NaNosenanotech chip to literally “sniff out” cancer tumors, was developed by Prof. Nir Peled of Tel Aviv University‘s Sackler Faculty of Medicine, Prof. Hossam Haick (inventor) of the TechnionIsrael Institute of Technology, and Prof. Fred Hirsch of the University of Colorado School of Medicine in Denver.
The study, presented at a recent American Society of Clinical Oncology conference in Chicago, was conducted on 358 patients who were either diagnosed with or at risk for lung cancer.


The smell of cancer

Lung cancer is a devastating disease, responsible for almost 2,000 deaths in Israel annually — a third of all cancer-related deaths,” said Dr. Peled. “Lung cancer diagnoses require invasive procedures such as bronchoscopies, computer-guided biopsies, or surgery. Our new device combines several novel technologies with a new concept — using exhaled breath as a medium of diagnosing cancer.”
Our NaNose was able to detect lung cancer with 90 percent accuracy even when the lung nodule was tiny and hard to sample. It was even able to discriminate between subtypes of cancer, which was unexpected,” said Dr. Peled.

Source: http://www.aftau.org/

Greek Mythology Helps Research Against Brain Cancer

An Indiana University School of Medicine breast cancer surgeon is pursuing research that will utilize glass, gold, nanotechnology and Greek mythology hoping to vanquish breast cancer that has metastasized to the brain. Susan E. Clare, M.D., Ph.D., associate professor of surgery at the IU School of Medicine, is the initiating principal investigator for a $573,000 Department of Defense grant that will allow her to explore a new approach to delivering therapy to brain metastases from primary breast cancer. As did the Greeks of old, Dr. Clare hopes to covertly deliver “warriorsto the enemy stronghold, in this case a metastatic brain tumor. Her research will explore using a cell from the body’s immune system to deliver chemotherapy directly to the brain metastases. The drug or other therapeutic is attached to the nanospheres, which are carried within the immune cell, much as soldiers were carried within the Trojan Horse. The immune cells travel in the bloodstream and release the drug when it has reached the tumor site.

brain metastasis
The problem for almost all drugs, and HER2-targeted drugs are no exception, is that the blood-brain barrier is a significant impediment to delivering therapies in concentrations that can be effective,” Dr. Clare said.

That biological issue caused Dr. Clare to explore other methods of delivering drugs to metastatic brain tumors. Using nanoparticles called “nanoshells,” developed by Naomi J. Halas, Ph.D., D.Sc., director of the Laboratory for Nanophotonics at Rice University, Dr. Clare hopes to target the brain tumors with lapatinib at a dose sufficient to shut down the signaling pathway needed for the cancer cells to proliferate.

Source: http://news.medicine.iu.edu