Translational Cancer Nano-Medicine: Multimodal Strategies to Overcome Tumor Drug Resistance

M. Amiji
Northeastern University, US

Summary:

Development of multidrug resistance (MDR) is a major challenge in clinical cancer medicine, where there are limited options for refractory patients often leading to fatal consequences. Over the past ten years, we have focused on the use of multimodal strategies that aim at improving drug delivery and residence to tumor mass as well as altering the resistant cell phenotype (e.g., tumor stem cells) in order to improve clinical outcomes. Based on our hypothesis that MDR develops due to the micro-environmental selection pressures induced by hypoxia, aerobic glycolysis, and the production of lactate that elevates cell-kill threshold, our approach relies on the use of combination therapeutic strategies with passive- and active-targeted nanocarrier-encapsulated agents. Specifically, I will present on: (1) co-administration of glucose metabolism inhibitor to overcome MDR with epidermal growth factor receptor targeted nanoparticle formulation, (2) modulation of intracellular ceramide to lower apoptotic threshold using a temporal-controlled nanoparticle formulation, and (3) the use of combination drug and siRNA co-therapy administered with combinatorial-designed nano-assemblies. In each of the example, our focus is to understand the medical challenge and then develop an effective solution for MDR. Special emphasis is placed on the use safe materials and scalable methods of nanocarrier fabrication in order to facilitate clinical translation and improve patient outcomes.