Project Title: Exploring the apoptotic property of Cytochrome c (Cyt c) for the development of anticancer Smart Nanoparticles
Research overview. During the past funding period we have developed a novel cytochrome c (Cyt c) based theranostic drug-delivery system. Decoration with the ligand folate enables this system to be selective towards cancer cells overexpressing the folate receptor. We have also recently used transferrin as ligand because of the overexpression of the transferrin receptor in many cancer cell lines. We have demonstrated that Cyt c delivery to the cytoplasm induces apoptosis thus overcoming inactivation of the upstream components of the cell death signaling pathways (such as the p53 pathway) that activate the release of cytochrome c (Cyt c) from the mitochondria to the cytoplasm in response to DNA damage. We have embarked on in vivo experiments and have shown that glioblastoma tumors in a mouse model significantly shrank. The REU students will have a variety of synthetic and mechanistic projects. Some students will work on optimizing the particle size, surface charge, and polarity of different labeled nanoparticles to promote maximum accumulation in the tumors. Other students will undertake mechanistic investigations to explore the mode of drug action and the uptake pathway. We will be able to determine which Cyt c site modifications allow for proteolytically stable conjugates, with potent activity, and cancer cell selectivity.