Mary Caldorera-Moore, B.S., M.S.
National Science Foundation Graduate Research Fellow
Office: BME 5.416
mcmoore@mail.utexas.edu

Research Focus: Nanofabrication of Stimuli Responsive Drug Delivery Nanoparticles

In recent years, a series of highly sophisticated drugs, rationally designed to target various cellular pathways have emerged. Most of these drugs interfere with key cellular processes and, like many of their currently used counterparts, are highly cytotoxic. Therefore, the ultimate clinical success of these agents lies in our ability to develop efficient and accurately targeted carrier vehicles that are capable of delivering therapeutic doses of drugs primarily to the diseased (e.g. tumor) cells while sparing their physiologically healthy neighbors. Strategies to significantly reduce, if not eliminate, systemic bystander effects related to anti-cancer therapy while at the same time delivering high doses of drugs to tumor cells could tremendously improve the high morbidity associated with these treatments. My research focuses on developing diseased responsive, drug delivery nanocarriers of specific shape, size, and aspect ratio, using a nanoimprinting lithography technique: Step and Flash Imprint Lithography (S-FIL). S-FIL allows for high-throughput fabrication of nanoparticles of precise geometries (shape, size, and aspect ratio). The ability to manipulate geometry and composition of nanoscale carriers is essential for controlling their in-vivo transport, bio-distribution, and release mechanism. Our goal is to create stimuli responsive nanocarriers of specific geometries, and to evaluate how particle geometry affects drug release profile, bio-distribution, and in-vivo transport. In my research I have successfully fabricated monodisperse, shape-specific, biodegradable nanocarriers with an environmentally sensitive penta-peptide GFLGK incorporated into the poly ethylene glycol diacrylate network. In this way, drugs can be released from the nanocarriers in the presence of Cathepsin B. Cathepsin B lysosomal cysteine proteases is highly over expressed (and locally secreted) in a variety of cancers including non-small cell lung cancer (NSCLC). We have generated uniform nanocarriers sub-50nm in size and also demonstrate encapsulation and controlled release from these nanoparticles only in the presence of Cathepsin B. The surfaces of these nanocarriers can be functionalized with cell targeting ligands. The incorporation of stimuli responsive peptide and target ligands on the surface of the particles provides a means for targeted drug release inside specific cellular compartments or under particular disease conditions, therefore providing a potential means for disease-controlled delivery.