Researchers receive $3M grant to develop targeted cancer drugs and repair damaged arteries

The National Institutes of Health has awarded grants totaling $3 million for two nanoparticle research projects in which Penn State bioengineer Jian Yang is co-principal investigator. Drawing upon biology and materials science, the researchers will develop new polymers designed to deliver targeted cancer drugs and repair damaged arteries.

Yang and co-PI Jer-Tsong Hsieh of the University of Texas Southwestern Medical Center received $1.6 million over five years to develop biodegradable nanoparticles to image and treat prostate cancer.

Prostate cancer is the second leading cause of cancer death in American men. If the cancer develops treatment resistance, the tumors grow and spread to other parts of the body. To prevent that, Yang and Hsieh will try to identify a prostate cancer-specific drug called a genotoxin that will attack the cancer cells, and also a fluorescent nanoparticle that targets those cancer cells.

Yang's group plans to add magnetic resonance imaging particles to the fluorescent nanoparticles in order to find the exact location of the tumor. If surgical removal of the cancer is required, fluorescent nanoparticles could attach to cancer cells and help the surgeon identify those small clusters of cancer cells that are usually invisible to the eye.

"We will need to optimize the genotoxin, and make sure we can put it into the nanoparticle," Yang said. "Then we will have to tune the nanoparticle to emit strong fluorescence, and also control the release of the drug into the tumor and not the bloodstream."

Yang and co-PI Kytai Truong Nguyen of the University of Texas Arlington received $1.4 million over four years to develop nanoparticles that promote healing in damaged endothelium, the lining of blood vessels, which can be injured in surgical procedures that unblock clogged arteries.

"Angioplasty and stenting often damage arterial walls, with a significant risk of subsequent complications, such as re-narrowing of the artery or blood clot," Yang said.

Platelets accumulate on the damaged vessel, initiating clot formation. Other cells can deposit on the damaged vessel wall, building up a blockage. The result is multiple traumatic angioplastic and stenting procedures.

The researchers propose to develop a polymer nanoparticle that mimics platelets in the blood that form the clot and create a cover over the damage. Their nanoparticle is decorated with a molecule called GP1b peptide that links to the injured vessel wall and with an anti-CD34 antibody that catches the circulating endothelial progenitor cells that can grow into mature endothelial cells. Over time, the nanoparticles will degrade harmlessly as the new blood vessel lining repairs the damage, avoiding the need for a stent.

A surgeon will still do angioplasty first, according to Yang, but not put in a stent. The nanoparticle solution will be injected instead.

"Once our nanoparticles attach to the vessel wall, the platelets cannot attach," Yang said. "The nanoparticles can outperform the platelets for vessel wall binding due to their smaller sizes. Then the nanoparticles will catch the circulating endothelial progenitor cells to repair the injured vessel wall.

Once their missions are done, the nanoparticles will simply disappear without causing any long-term toxicity. These injectable nanoparticles have worked well in animal models in studies with our collaborators at UT Arlington."