Polymer Nanoparticle Locates And Treats Breast Tumors

One major problem in treating cancer is identifying the location of small tumors and treating them before they metastasize.

In an effort to overcome that problem, researchers at Wake Forest Baptist Medical Center have developed a fluorescing nanoparticle capable of finding tumors, lighting up upon arrival and being activated with light to generate heat to destroy the cancer cells.

A study in which these nanoparticlesHybrid Donor-Acceptor Polymer Particles, or H-DAPPs – successfully located and killed breast cancer skills in mice is published in the current issue of the journal ACS Applied Materials and Interfaces.

An unexpected result was how efficiently the nanoparticles localized to the tumors without any targeting agent,” said the study’s lead author, Nicole Levi-Polyachenko, Ph.D., associate professor of plastic and reconstructive surgery at Wake Forest School of Medicine, part of Wake Forest Baptist. “Achieving high enough levels of H-DAPPs within the tumor to allow it to be seen provides an advantage for knowing exactly where light should be applied to generate heat and kill the cancer cells.

Other investigators have developed nanoparticles to detect tumors or carry drugs, and Levi-Polyachenko’s team has created polymers that strongly absorb infrared light and generate heat. Regarding the new nanoparticle, she said, “It was exciting to figure out the step for combining a heat-generating polymer with a light-emitting polymer to allow for detection and on-demand heat treatment.

H-DAPPs are made of electrically conductive polymers and are smaller than 100 nanometers (0.00000393701 of an inch) in diameter. Their small size and soft composition makes it easy for them to travel through the bloodstream to the tumor.

There is much more research needed to ensure that H-DAPPs can safely be used in humans,” Levi-Polyachenko said. “But we are enthusiastic about exploring the use of H-DAPPs with other cancer types and eventually in patients.

Source: http://www.wakehealth.edu/

Blood Test for Early Detection of Pancreatic Cancer

A newly identified biomarker panel could pave the way to earlier detection and better treatment for pancreatic cancer, according to new research from the Perelman School of Medicine at University of Pennsylvania. Currently over 53,000 people in the United States are diagnosed with pancreatic cancer — the fourth leading cause of cancer death — every year. The blood biomarkers, detailed today in Science Translational Medicine, correctly detected pancreatic cancer in blood samples from patients at different stages of their disease.

The majority of pancreatic cancer patients are not diagnosed until an advanced stage, beyond the point at which their tumors can be surgically removed.

A team led by Ken Zaret, PhD, director of the Penn Institute for Regenerative Medicine and the Joseph Leidy Professor of Cell and Developmental Biology, and Gloria Petersen, PhD, from the Mayo Clinic, identified a pair of biomarkers that physicians could soon use to discover the disease earlier.

Starting with our cell model that mimics human pancreatic cancer progression, we identified released proteins, then tested and validated a subset of these proteins as potential plasma biomarkers of this cancer,” Zaret said. The authors anticipate that health care providers will use the early-detection biomarkers to test for their presence and levels in blood from pancreatic cancer patients and blood drawn from individuals with a high risk of developing pancreatic cancer, including those who have a first-degree relative with pancreatic cancer, are genetically predisposed to the disease, or who had a sudden onset of diabetes after the age of 50.

Early detection of cancer has had a critical influence on lessening the impact of many types of cancer, including breast, colon, and cervical cancer. A long standing concern has been that patients with pancreatic cancer are often not diagnosed until it is too late for the best chance at effective treatment,” said Robert Vonderheide, MD, DPhil, director of the Abramson Cancer Center (ACC) at the University of Pennsylvania. “Having a biomarker test for this disease could dramatically alter the outlook for these patients.”

Source: https://www.pennmedicine.org/

Nanoparticles And Immunotherapy, Allies To Eradicate Cancer

Some researchers are working to discover new, safer ways to deliver cancer-fighting drugs to tumors without damaging healthy cells. Others are finding ways to boost the body’s own immune system to attack cancer cells. Researchers at Pennsylvania State University   (Penn State) have combined the two approaches by taking biodegradable polymer nanoparticles encapsulated with cancer-fighting drugs and incorporating them into immune cells to create a smart, targeted system to attack cancers of specific types.


The traditional way to deliver drugs to tumors is to put the drug inside some type of nanoparticle and inject those particles into the bloodstream,” said Jian Yang, professor of biomedical engineering, Penn State. “Because the particles are so small, if they happen to reach the tumor site they have a chance of penetrating through the blood vessel wall because the vasculature of tumors is usually leaky.”

The odds of interacting with cancer cells can be improved by coating the outside of the nanoparticles with antibodies or certain proteins or peptides that will lock onto the cancer cell when they make contact. However, this is still a passive drug delivery technology. If the particle does not go to the tumor, there is no chance for it to bind and deliver the drug.

Yang and Cheng Dong, professor of biomedical engineering, wanted a more active method of sending drugs to the cancer wherever it was located, whether circulating in the blood, the brain, or any of the other organs of the body.

“I have 10 years of working in immunology and cancer,” Dong said. “Jian is more a biomaterials scientist. He knows how to make the nanoparticles biodegradable. He knows how to modify the particles with surface chemistry, to decorate them with peptides or antibodies. His material is naturally fluorescent, so you can track the particles at the same time they are delivering the drug, a process called theranostics that combines therapy and diagnostics. On the other hand, I study the cancer microenvironment, and I have discovered that the microenvironment of the tumor generates kinds of inflammatory signals similar to what would happen if you had an infection.”

Immune cells, which were built to respond to inflammatory signals, will be naturally attracted to the tumor site. This makes immune cells a perfect active delivery system for Yang’s nanoparticles. The same technology is also likely to be effective for infectious or other diseases, as well as for tissue regeneration, Dong said.

Source: http://news.psu.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.


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/

Light-Controlled NanoRobot Attacks Tumors

A team of researchers led by Dr Jinyao Tang of the Department of Chemistry, the University of Hong Kong, has developed the world’s first light-seeking synthetic Nano robot. With size comparable to a blood cell, those tiny robots have the potential to be injected into patients’ bodies, helping surgeons to remove tumors and enabling more precise engineering of targeted medications.

It has been a dream in science fiction for decades that tiny robots can fundamentally change our daily life. The famous science fiction movie “Fantastic Voyage” is a very good example, with a group of scientists driving their miniaturized Nano-submarine inside human body to repair a damaged brain. In the film “Terminator 2”, billions of Nanorobots were assembled into the amazing shapeshifting body: the T-1000.


“Light is a more effective option to communicate between microscopic world and macroscopic world. We can conceive that more complicated instructions can be sent to Nanorobots which provide scientists with a new tool to further develop more functions into Nanorobot and get us one step closer to daily life applications”

The Nobel Prize in Chemistry 2016 was awarded to three scientists for “the design and synthesis of molecular machines”. They developed a set of mechanical components at molecular scale which may be assembled into more complicated Nano machines to manipulate single molecule such as DNA or proteins in the future. The development of tiny nanoscale machines for biomedical applications has been a major trend of scientific research in recent years. Any breakthroughs will potentially open the door to new knowledge and treatments of diseases and development of new drugs.

One difficulty in Nanorobot design is to make these nanostructures sense and respond to the environment. Given each Nanorobot is only a few micrometer in size which is ~50 times smaller than the diameter of a human hair, it is very difficult to squeeze normal electronic sensors and circuits into Nanorobots with reasonable price. Currently, the only method to remotely control Nanorobots is to incorporate tiny magnetic inside the Nanorobot and guide the motion via external magnetic field.

The Nanorobot developed by Dr Tang’s team use light as the propelling force, and is the first research team globally to explore the light-guided Nanorobot and demonstrate its feasibility and effectiveness. In their paper published in Nature Nanotechnology, Dr Tang’s team demonstrated the unprecedented ability of these light-controlled Nanorobots as they are “dancing” or even spell a word under light control. With a novel Nanotree structure, the Nanorobots can respond to the light shining on it like moths being drawn to flames. Dr Tang described the motions as if “they can “see” the light and drive itself towards it”.

The findings have been published in the scientific journal Nature Nanotechnology.

Source: http://www.hku.hk/

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/

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/

Nanoparticle-Based Cancer Therapies Shown to Work in Humans

A team of researchers led by Caltech scientists has shown that nanoparticles can function to target tumors while avoiding adjacent healthy tissue in human cancer patients.

nanoparticle against brain cancer

Our work shows that this specificity, as previously demonstrated in preclinical animal studies, can in fact occur in humans“, says study leader Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech. “The ability to target tumors is one of the primary reasons for using nanoparticles as therapeutics to treat solid tumors.
The scientists demonstrate that nanoparticle-based therapies can act as a “precision medicine” for targeting tumors while leaving healthy tissue intact. In the study, Davis and his colleagues examined gastric tumors from nine human patients both before and after infusion with a drug—camptothecin—that was chemically bound to nanoparticles about 30 nanometers in size.

Our nanoparticles are so small that if one were to increase the size to that of a soccer ball, the increase in size would be on the same order as going from a soccer ball to the planet Earth,” says Davis, who is also a member of the City of Hope Comprehensive Cancer Center in Duarte, California, where the clinical trial was conducted.

The team found that 24 to 48 hours after the nanoparticles were administered, they had localized in the tumor tissues and released their drug cargo, and the drug had had the intended biological effects of inhibiting two proteins that are involved in the progression of the cancer. Equally important, both the nanoparticles and the drug were absent from healthy tissue adjacent to the tumors.

The findings, have been published online in the journal Proceedings of the National Academy of Sciences.

Source: https://www.caltech.edu/

Multi-Tasking Nanoparticle to Kill Cancer

Kit Lam and colleagues from UC Davis and other institutions have created dynamic nanoparticles (NPs) that could provide an arsenal of applications to diagnose and treat cancer. Built on an easy-to-make polymer, these particles can be used as contrast agents to light up tumors for MRI and PET scans or deliver chemo and other therapies to destroy tumors. In addition, the particles are biocompatible and have shown no toxicity.
multitask_nanoparticles (1
These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors; apply light to make the nanoparticles release singlet oxygen (photodynamic therapy) or use a laser to heat them (photothermal therapy) – all proven ways to destroy tumors.”
Jessica Tucker, program director from the National Institute of Biomedical Imaging and Bioengineering, said the approach outlined in the study has the ability to combine both imaging and therapeutic applications in a single platform, which has been difficult to achieve, especially in an organic, and therefore biocompatible, vehicle.

This is especially valuable in cancer treatment, where targeted treatment to tumor cells, and the reduction of lethal effects in normal cells, is so critical,” she added.
The study was published online today in Nature Communications.
Source: http://www.ucdmc.ucdavis.edu/

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.


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/

How To Target Pancreatic Cancer

Short, customized carbon nanotubes have the potential to deliver drugs to pancreatic cancer cells and destroy them from within, according to researchers, led by Andrew Barron, chemist at Rice University and the University of Texas MD Anderson Cancer Center. Pristine nanotubes produced through a new process developed at Rice can be modified to carry drugs to tumors through gaps in blood-vessel walls that larger particles cannot fit through. The nanotubes may then target and infiltrate the cancerous cells’ nuclei, where the drugs can be released through sonication – that is, by shaking them. The next step was to cut the nanotubes down to size. Very long nanotubes are floppy and hard to deal with, Barron said. Enrico Andreoli, a postdoctoral research associate in Barron’s group and lead author of the paper, used a thermal process to chop them to an average length of 50 nanometers. (A human hair is about 100,000 nanometers wide.)

Instead of ending up with a fluffy nanotube powder, we get something that looks like a hockey puck,” Barron said. “It’s not dense – it looks like a spongy puck – but you can cut it with a razor blade. You can weigh it and do accurate chemistry with it.”
Fleming, whose work focuses on improving drug delivery for pancreatic cancer, cautioned that more research is required. ”The next step will be to test this approach in mice that have allografts taken from human tumors,” he said. “The architecture of these tumors will more closely resemble that of human pancreatic cancer.”

The research was reported in the Royal Society of Chemistry’s Journal of Materials Chemistry B.
Source: http://news.rice.edu/

How To Kill Cancerous Cells Instantaneously

The first preclinical study of a new Rice University – developed anti-cancer technology found that a novel combination of existing clinical treatments can instantaneously detect and kill only cancer cells — often by blowing them apart — without harming surrounding normal organs. The work was conducted by researchers from Rice, the University of Texas MD Anderson Cancer Center and Northeastern University.

The first preclinical study of the anti-cancer technology “quadrapeutics” found it to be 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumors

We address aggressive cancers that cannot be efficiently and safely treated today,” said Rice scientist Dmitri Lapotko, the study’s lead investigator. “Surgeons often cannot fully remove tumors that are intertwined with important organs. Chemotherapy and radiation are commonly used to treat the residual portions of these tumors, but some tumors become resistant to chemoradiation. Quadrapeutics steps up when standard treatments fail. At the same time, quadrapeutics complements current approaches instead of replacing them.”

The research is available in the online journal Nature Medicine.
Source: http://news.rice.edu/