Targeted Delivery of a Mitochondriotropic Apoptosis Modulator Using Multifunctional Polymeric Nanoparticles for the Treatment of Drug Resistant Tumors

Student: Lara Milane
Department: Pharmaceutical Sciences
Advisor: Mansoor Amiji

Abstract

Mitochondria are well recognized as the central organelles of energy production and the apoptotic pathway. Mitochondrial dysfunction contributes to the pathogenesis of a multitude of conditions including neurodegeneration, obesity, diabetes, and cancer. The significance of mitochondria in maintaining cellular homeostasis is exemplified in the disease state of cancer which is the uncontrolled proliferation of cells – cells which fail to undergo apoptosis. The successful treatment of cancer is often obstructed by the development of multidrug resistance (MDR); current clinical therapies are ineffective at treating MDR cancer as MDR cancer cells evade the arsenal of common chemotherapeutic agents.

The objective of this project is the development of a targeted delivery system for the co-administration of a mitochondriotropic apoptosis modulator and a common chemotherapeutic agent for the treatment of MDR cancer. The apoptosis modulator will be used to reduce the apoptotic threshold of MDR cancer cells rendering the tumor vulnerable to the chemotherapeutic. The overexpression of EGFR will be exploited to achieve cancer-cell specific targeting of the multifunctional nanoparticles.