Award-Winning Pharmaceutical Sciences Research
The research proposal of faculty member Terrick Andey, PhD, “Nanoparticle Delivery Platform for Dual Targeting of Triple-Negative Breast Cancer,” won him the American Association of Colleges of Pharmacy’s New Investigator Award in 2018. Now, his research is ready to be published.
Dr. Terrick Andey, Associate Professor of Pharmaceutical Sciences and Assistant Dean of Graduate Studies for MCPHS, School of Pharmacy - Worcester/Manchester, was one of just sixteen researchers nationwide honored by the American Association of Colleges of Pharmacy (AACP) in 2018 with the New Investigator Award. The research for which he was awarded, “Nanoparticle Delivery Platform for Dual Targeting of Triple-Negative Breast Cancer,” has since developed and is now ready for submission; he plans to submit his data to publishers within the coming months. Dr. Andey’s drug delivery system is both comprehensive and versatile (it is compatible with various therapies), and the publication of his findings could lead to exciting changes in the world of oncology treatment.
Triple-Negative Breast Cancer (TNBC) makes up 10-20% of breast cancers. TNBC is defined as cancer without estrogen receptors, progesterone receptors, and the HER2 protein (the HER2 protein may be present, but at an extremely low level). The lack of these three receptors makes it difficult to treat this type of cancer because common treatments, like hormonal therapies and HER2-targeted therapies, would have little to no effect on a TNBC tumor. Further complicating treatment options is how the nature of the cell is often basal-like (resembling cells lining the breast duct), which is a more aggressive cell type.
Circumventing these obstacles, Dr. Andey’s method of drug delivery involves the use of tumor-targeting liposomes. Although it was considered a novel approach in the proposal, Dr. Andey’s use of liposomes dates back to 2011, when he was in graduate school. Liposomes are synthetic vesicles, or pore-like structures inspired by the lipid bilayer of the cell membrane. It is because of this lipid bilayer that Dr. Andey can use nano-sized liposomes (nanoliposomes) to carry a drug (chemotherapy, peptide, DNA, or RNA) and trick the tumor into accepting it. “We essentially are able to present the drug delivery system to the specific tumor site, which is facilitated by a ligand—a marker on the surface of the formulation—that would then act in the similar manner as a lock and key with the receptor on the surface of the tumor,” he explains. The ligands, or molecules that bind with the tumor surface marker or receptor, can be changed to target different types of cancers. “So, we are exploiting some of the markers on the surface of the tumor for targeting of our drug formulation,” he says. “And there could be so many other factors.” For this study, the ligand that Dr. Andey uses is hyaluronic acid, which targets a receptor expressed on TNBC cells called CD44.
The dual-targeting component of Dr. Andey’s research is representative of the delivery system’s targeting (the CD44 receptor) as well as the therapeutic targeting. The latter is facilitated by the two small interfering RNA (siRNA) therapies that Dr. Andey uses with his delivery system, which target separate gene expressions: PPARD and HMGA1. “Those two genes, PPARD and HMGA1, have been shown to be oncogenic, so they promote the tumorigenic state. So, the idea was to essentially silence them, and that’s why we use the small interfering RNA,” he says.
In addition to the innovative method of dual targeting, Dr. Andey has used the novel approach of simulating the tumor microenvironment (TME) in order to more accurately test the TNBC cells’ resistance to the two therapies. According to Dr. Andey, many preclinical and lab-based experiments can have misleadingly “successful” results because they do not account for the biological environment—consider the difference of growing cells in the tumor microenvironment versus an in-vitro environment like home-field advantage. In mimicking the TME, Dr. Andey said the cells became more resistant: “And so the results of that therapy, once we do the targeting, would much more closely align with what we would see in the biological system than if you would just grow the cells in a plate.” In other words, Dr. Andey created a greenhouse of sorts for the TNBC cells to grow as they typically would in their natural environment, thus projecting realistic laboratory results and expectations for human trials.
Dr. Andey’s research could lead to life-changing treatments for cancer patients: The targeted, formulation approach of his drug delivery system reduces the exposure and effect on normal cells as compared to chemotherapy, which diffuses into all cells. Another reason for his drug delivery system to affect cancer cells more than normal cells is because of the aggressive nature of TNBC. TNBC tumors grow quickly and with large pores, which his nanoparticles can sneak through to deposit the drugs. Dr. Andey’s research, aided by an MCPHS student pursuing a Master of Science in Pharmaceutics and a Doctor of Philosophy in Pharmacology student, could change the prospects for one of the most difficult cancers to treat.