New Research from Penn Engineering and MIT Shows How Nanoparticles Can Turn Off Genes in Bone Marrow

Michael Mitchell
Michael Mitchell, PhD

by Evan Lerner

Using specialized nanoparticles, researchers from Penn Engineering and the Massachusetts Institute of Technology (MIT) have developed a way to turn off specific genes in cells of bone marrow, which play an important role in producing blood cells. These particles could be tailored to help treat heart disease or to boost the yield of stem cells in patients who need stem cell transplants.

This type of genetic therapy, known as RNA interference, is usually difficult to target to organs other than the liver, where nanoparticles would tend to accumulate. The researchers were able to modify their particles in such a way that they would accumulate in the cells found in the bone marrow.

In a recent Nature Biomedical Engineering study, conducted in mice, the researchers showed that they could use this approach to improve recovery after a heart attack by inhibiting the release of bone marrow blood cells that promote inflammation and contribute to heart disease.

“If we can get these particles to hit other organs of interest, there could be a broader range of disease applications to explore, and one that we were really interested in in this paper was the bone marrow. The bone marrow is a site for hematopoiesis of blood cells, and these give rise to a whole lineage of cells that contribute to various types of diseases,” says Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, one of the lead authors of the study.

Marvin Krohn-Grimberghe, a cardiologist at the Freiburg University Heart Center in Germany, and Maximilian Schloss, a research fellow at Massachusetts General Hospital (MGH), are also lead authors on the paper, which appears today in Nature Biomedical Engineering. The paper’s senior authors are Daniel Anderson, a professor of Chemical Engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and Matthias Nahrendorf, a professor of Radiology at MGH.

Mitchell’s expertise is in the design of nanoparticles and other drug delivery vehicles, engineering them to cross biological barriers that normally block foreign agents. In 2018, he received the NIH Director’s New Innovator Award to support research on delivering therapeutics to bone marrow, a key component of this new study.

The researchers have shown they can deliver nanoparticles to the bone marrow, influencing their function with RNA silencing. At top right, the bone marrow is not yet treated with particles that turn off a gene called SDF1. At bottom right, the number of neutrophils (blue) decreases, indicating that they have been released from bone marrow after treatment. At left, treatment with a control nanoparticle does not affect the number of neutrophils before and after treatment.

Read the full story at Penn Engineering Today.

Penn Bioengineering Postdoc Rachel Riley Named Assistant Professor at Rowan University

Rachel Riley, Ph.D.

The Department of Bioengineering is proud to congratulate Postdoctoral Fellow Rachel Riley on her appointment as an Assistant Professor in Biomedical Engineering at Rowan University starting September 2020.

Originally from Matawan, NJ, Riley has been an NIH Postdoctoral Fellow in the Mitchell Lab since 2018. Her move to a faculty position at Rowan marks a return, as she received her B.S. in Civil and Environmental Engineering there in 2012. Riley went on to receive her Ph.D. in Biomedical Engineering in 2018 at the University of Delaware with Emily Day, Ph.D. before joining the lab of Michael J. Mitchell, Ph.D., Skirkanich Assistant Professor of Innovation, later that year. The Mitchell Lab’s research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers.

“Rachel has had a prolific academic career at the University of Delaware and at Penn, launching several exciting research projects and mentoring the next generation of STEM researchers,” Mitchell says. “I’m very hopeful that her new position as an Assistant Professor of Biomedical Engineering at Rowan University will permit her to engineer new drug delivery technologies for women’s health applications.”

Research in the Riley Lab at Rowan will explore how nanoparticle drug delivery technologies can be engineered specifically for applications in women’s health. They will use nanoparticles as tools to study and treat gynecological cancers, fetal diseases, and pregnancy complications. Riley’s ultimate goal is to gain a fundamental understanding of how nanoparticle structure influences delivery to gynecological tissues to enable them to take an engineering approach to tackle new applications in women’s health.

Riley says that she is committed to supporting women and minorities in STEM disciplines and she looks forward to continuing collaborations with Penn and starting new collaborations with researchers at Cooper Medical School at Rowan University (CMSRU). Congratulations, Dr. Riley!

Oncology/Engineering Review Published

oncology
Mike Mitchell, Ph.D.

Michael Mitchell, Ph.D., who will arrive in the Spring 2018 semester as assistant professor in the Department of Bioengineering, is the first author on a new review published in Nature Reviews Cancer on the topic of engineering and the physical sciences and their contributions to oncology. The review was authored with Rakesh K. Jain, Ph.D., who is Andrew Werk Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School, and Robert Langer, Sc.D., who is Institute Professor in Chemical Engineering at the David H. Koch Institute for Integrative Cancer Research at MIT. Dr. Mitchell is currently in his final semester as a postdoctoral fellow at the Koch Institute and is a member of Dr. Langer’s lab at MIT.

The review focuses on four key areas of development for oncology in recent years: the physical microenvironment of the tumor; technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. Asked about the review, Dr. Mitchell said, “We’ve seen exponential growth at the interface of engineering and physical sciences over the last decade, specifically through these advances. These novel tools and technologies have not only advanced our fundamental understanding of the basic biology of cancer but also have accelerated the discovery and translation of new cancer therapeutics.”