As the guardian of the brain, the blood-brain barrier (BBB) denies entry to infection-causing toxins and pathogens, while at the same time granting access to healthy nutrients. The flip side of this protection is that the BBB can do its job too well – like when it blocks life-saving cancer drugs. The inability of therapeutics to get past the BBB is why brain cancer is often treated with invasive surgery instead of medicine, but Syracuse University researchers are working to change that.

Davoud Mozhdehi, assistant professor of chemistry, is the recipient of a Ralph E. Powe Junior Faculty Enhancement Award to investigate a nanoparticle that could “trick” its way into the brain, resulting in a novel method of drug delivery.

Mozhdehi and his collaborator Shikha Nangia, associate professor of biomedical and chemical engineering in the College of Engineering and Computer Science, are working with the protein claudin-5, which acts as the gatekeeper in the BBB. Nangia has identified sections of that protein that are responsible for maintaining its barrier properties. By attaching fragments of claudin-5 to the surface of a computer-designed nanoparticle, Mozhdehi and Ph.D. student Md. Shahadat Hossain hope to create a particle that could carry a drug into and through the blood-brain barrier, like a Trojan Horse. The nanoparticle is in a sense disguising itself with claudin-5 fragments in order to fit in with the rest of the barrier proteins.

“When the nanoparticle, attached to a drug, gets to the BBB, it can mix undetected with the barrier,” says Mozhdehi. “That gives it a ‘pass’ to deliver the drug into the brain.”

Both Mozhdehi and Nangia are members of the BioInspired Institute and the Syracuse Biomaterials Institute. These interdisciplinary faculty working groups develop and design programmable smart materials to address global challenges in health, medicine and materials innovation. Their applied research on this project aligns with each group’s mission to promote collaboration on the design of substances to treat the human body.

In the coming months, Mozhdehi and Hossain will produce the nanoparticle and have it tested at Oak Ridge National Laboratory in Tennessee. Before the pandemic, Hossain had planned to travel to Oak Ridge and work with Dr. Shuo Qian, staff scientist at ORNL, to evaluate the substance’s stability using the lab’s powerful X-ray machine. Instead, collaborators at the lab will run the experiment and send back the results. Mozhdehi and Hossain will then analyze the data and determine the feasibility of designing a nanoparticle for the next stage of experimental studies.

Mozhdehi’s grant was funded by Oak Ridge Associated Universities (ORAU), a consortium of over 120 Universities providing innovative scientific and technical solutions to advance national priorities in science, education, security and health, and is being matched by the College of Arts and Sciences and the Office of Research. ORAU has awarded 35 competitive research grants through the company’s Ralph E. Powe Junior Faculty Enhancement Awards program, which provides funds to enrich the research and professional growth of young faculty. The awards, now in their 30th year, are named for the late Ralph E. Powe, who served as the ORAU councilor from Mississippi State University for 16 years.