Nanoparticle Shrinks Breast Tumor, Prevent Recurrence

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. A mice that received an injection with the nanoparticle showed a 70 to 80 percent reduction in tumor size. Most significantly, mice treated with these nanoparticles showed resistance to future tumor recurrence, even when exposed to cancer cells a month later.

The results show that the newly designed nanoparticle produced potent anti-tumor immune responses to HER2-positive breast cancers. Breast cancers with higher levels of HER2 protein are known to grow aggressively and spread more quickly than those without the mutation.

In this proof-of-concept study, we were astounded to find that the animals treated with these nanoparticles showed a lasting anti-cancer effect,” says Betty Y.S. Kim, M.D., Ph.D., principal investigator, and a neurosurgeon and neuroscientist who specializes in brain tumors at Mayo Clinic’s Florida campus. “Unlike existing cancer immunotherapies that target only a portion of the immune system, our custom-designed nanomaterials actively engage the entire immune system to kill cancer cells, prompting the body to create its own memory system to minimize tumor recurrence. These nanomedicines can be expanded to target different types of cancer and other human diseases, including neurovascular and neurodegenerative disorders.”

Dr. Kim’s team developed the nanoparticle, which she has named “Multivalent Bi-specific Nano-Bioconjugate Engager,” a patented technology with Mayo Clinic Ventures, a commercialization arm of Mayo Clinic.

The findings have been published in Nature Nanotechnology.

Source: https://newsnetwork.mayoclinic.org/

Nanoparticles Overcome Treatment-Resistant Breast Cancer

Researchers at the University of Cincinnati (UC) College of Medicine have been able to generate multifunctional RNA nanoparticles that could overcome treatment resistance in breast cancer, potentially making existing treatments more effective in these patients. The research team  led by Xiaoting Zhang, PhD, associate professor at the UC College of Medicine, demonstrates that using a nanodelivery system to target HER2-positive breast cancer and stop production of the protein MED1 could slow tumor growth, stop cancer from spreading and sensitize the cancer cells to treatment with tamoxifen, a known therapy for estrogen-driven cancer.
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Most breast cancers express estrogen receptors, and the anti-estrogen drug tamoxifen has been widely used for their treatment,” says Zhang, who is also a member of the Cincinnati Cancer Center and the UC Cancer Institute. “Unfortunately, up to half of all estrogen receptor-positive tumors are either unresponsive or later develop resistance to the therapy. In this study, we have developed a highly innovative design that takes advantage of the co-overexpression of HER2 and MED1 in these tumors.”
Zhang and researchers in his lab found that these RNA nanoparticles were able to selectively bind to HER2-overexpressing breast tumors, eliminating MED1 expression and significantly decreasing estrogen receptor-controlled target gene production. The RNA nanoparticles not only reduced the growth and spread of the HER2-overexpressing breast cancer tumors, but also sensitized them to tamoxifen treatment.

The study, has been published in the online edition of ACS Nano.

Source: http://healthnews.uc.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/

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.


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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/

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.
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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/

Nanoflowers Deliver Drugs To Cancer Cells

Biomedical engineering researchers have developed daisy-shaped, nanoscale structures that are made predominantly of anti-cancer drugs and are capable of introducing a “cocktail” of multiple drugs into cancer cells. The researchers are all part the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill.
To make the “nanodaisies,” the researchers begin with a solution that contains a polymer called polyethylene glycol (PEG). The PEG forms long strands that have much shorter strands branching off to either side. Researchers directly link the anti-cancer drug camptothecin (CPT) onto the shorter strands and introduce the anti-cancer drug doxorubicin (Dox) into the solution. Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. Once in a cancer cell, the drugs are released.

Early tests of the “nanodaisy” drug delivery technique show promise against a number of cancers
We found that this technique was much better than conventional drug-delivery techniques at inhibiting the growth of lung cancer tumors in mice,” says Dr. Zhen Gu, senior author of the paper. “And based on in vitro tests in nine different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian and brain cancers.”
Source: http://news.ncsu.edu/

How 2 Drugs Knock Out Aggressive Tumors

MIT researchers have devised a novel cancer treatment that destroys tumor cells by first disarming their defenses, then hitting them with a lethal dose of DNA damage.
In studies with mice, the research team showed that this one-two punch, which relies on a nanoparticle that carries two drugs and releases them at different times, dramatically shrinks lung and breast tumors. The MIT team, led by Michael Yaffe, the David H. Koch Professor in Science, and Paula Hammond, the David H. Koch Professor in Engineering, describe the findings in the online journal Science Signaling.


Differential cell responses to chemotherapy treatment. The photo shows a range of responses of similar cells to the chemotherapeutic drug doxorubicin. The most intensely responding drugs are shown in yellow, many of which will die. Green cells are alive but not dividing. Red cells are continuing to grow and divide. Yaffe and colleagues have figured out how to increase the proprotion of triple negative breast cancer cells that can be killed by a specific time-ordered regiment of growth factor inhibitors and chemotherapy, with direct application to clinical treatment
I think it’s a harbinger of what nanomedicine can do for us in the future,” says Hammond, who is a member of MIT’s Koch Institute for Integrative Cancer Research. “We’re moving from the simplest model of the nanoparticle — just getting the drug in there and targeting it — to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumor.”

Source: http://newsoffice.mit.edu/

How To Measure Cancer In Living Cells

Purdue University researchers have developed a way to detect and measure cancer levels in a living cell by using tiny gold particles with tails of synthetic DNA. A team led by Joseph Irudayaraj, professor of agricultural and biological engineering, used gold nanoparticles to target and bind to fragments of genetic material known as BRCA1 messenger RNA splice variants, which can indicate the presence and stage of breast cancer. The number of these mRNA splice variants in a cell can be determined by examining the specific signal that light produces when it interacts with the gold nanoparticles.

A single gold nanoparticle, or monomer, appears green when illuminated (top left), while a pair of gold nanoparticles bound to an mRNA splice variant, or dimer, appears reddish (top right). Monomers and dimers also scatter light differently, as shown in the graph above

This is a simple yet sophisticated technique that can be used to detect cancer in a single cell and determine how aggressive it is,” said Irudayaraj, who is also the deputy director of the Bindley Bioscience Center. “Being able to quantify these genetic molecules could ultimately help clinicians provide better and more individualized treatment to cancer patients.”

The technique also could increase our understanding of cell biology and paves the way for genetic profiling and diagnosis based on a single cell, Irudayaraj said.
Source: http://www.purdue.edu/

Nanoparticles Carry 2 Different Cancer-killing Drugs

Researchers have developed a technique for creating nanoparticles that carry two different cancer-killing drugs into the body and deliver those drugs to separate parts of the cancer cell where they will be most effective. The technique was developed by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.
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In testing on laboratory mice, our technique resulted in significant improvement in breast cancer tumor reduction as compared to conventional treatment techniques,” says Dr. Zhen Gu, senior author of a paper on the research and an assistant professor in the joint biomedical engineering program at NC State and UNC-Chapel Hill.
We designed this drug delivery vehicle using a ‘programmed’ strategy,” says Tianyue Jiang, a lead author in Dr. Gu’s lab. “Different drugs can be released at the right time in their right places,” adds Dr. Ran Mo, a postdoctoral researcher in Gu’s lab and the other lead author.
Source: http://news.ncsu.edu/

“All-In-One Tool” Janus Against Cancer

University of Cincinnati researchers have developed a unique nanostructure that can, because of its dual-surface structure, serve as an improved “all-in-one tool” against cancer. A unique nanostructure developed by a team of international researchers, including those at the University of Cincinnati, promises improved all-in-one detection, diagnoses and drug-delivery treatment of cancer cells. The first-of-its-kind nanostructure is unusual because it can carry a variety of cancer-fighting materials on its double-sided (Janus) surface and within its porous interior. Because of its unique structure, the nano carrier can do all of the following:
Transport cancer-specific detection nanoparticles and biomarkers to a site within the body, e.g., the breast or the prostate. This promises earlier diagnosis than is possible with today’s tools.
Attach fluorescent marker materials to illuminate specific cancer cells, so that they are easier to locate and find for treatment, whether drug delivery or surgery.
Deliver anti-cancer drugs for pinpoint targeted treatment of cancer cells, which should result in few drug side effects. Currently, a cancer treatment like chemotherapy affects not only cancer cells but healthy cells as well, leading to serious and often debilitating side effects.
nanostructure all-in-one-tool The first-of-its-kind nanostructure is unusual because it can carry a variety of cancer-fighting materials on its double-sided (Janus) surface and within its porous interior

In this effort, we’re using existing basic nano systems, such as carbon nanotubes, graphene, iron oxides, silica, quantum dots and polymeric nano materials in order to create an all-in-one, multidimensional and stable nano carrier that will provide imaging, cell targeting, drug storage and intelligent, controlled drug release,” said UC’s Professor of materials science and engineering Shi, adding that the nano carrier’s promise is currently greatest for cancers that are close to the body’s surface, such as breast and prostate cancer.
Source: http://www.uc.edu/

How To Eradicate Ovarian Cancer

Ovarian cancer is the deadliest of all gynecological cancers. According to the American Cancer Society 14,000 women will die this year from ovarian cancer. A new treatment have been designed by researchers from the Florida International University Herbert Wertheim College of Medicine and the FIU College of Engineering and Computing what could be a breakthrough. This novel way to deliver cancer-killing drugs using nanotechnology results from a codllaboration between an oncologist and an engineer looking to challenge the odds and save lives.
In their lab experiments, Taxol, a chemotherapy drug used to treat ovarian cancer, was loaded onto a magneto-electric nanoparticle, and using an electric field the drug penetrated into the tumor cells completely destroying the tumor within 24 hours, while sparing normal ovarian cells.
Carolyn D. Runowicz

Sparing healthy cells has been a major challenge in the treatment of cancer, especially with the use of Taxol; so in addition to treating the cancer, this could have a huge impact on side-effects and toxicity,” said Carolyn Runowicz, M.D., professor of gynecology and obstetrics and executive dean for academic affairs at the Herbert Wertheim College of Medicine. “This is an important beginning for us. I’m very excited because I believe that it can be applied to other cancers including breast cancer and lung cancer,” added Sakhrat Khizroev, Ph.D., professor of electrical and computer engineering at the FIU College of Engineering and Computing.

Source: http://news.fiu.edu/

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.

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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