(135c) Synthesis and Evaluation of Peptide-Functionalized Polymersomes for Targeted Drug Delivery to Colon Cancer Cells

Recently, polymersomes (polymeric vesicles) have gained increased attention as systemic drug delivery vehicles due to their exceptional mechanical stability and increased stealth properties compared to pegylated liposomes. Self-assembled from amphiphilic block copolymers, polymersomes contain a hydrophobic core (e.g., polybutadiene) and a hydrophilic corona (usually poly(ethylene oxide) or PEO). This combination offers a host of advantages. Our goal is to bring biofunctionality to polymersomes in order to facilitate their potential use as a drug delivery agent. To improve the selectivity of the polymersome for different therapies, a novel peptide synthesized in our lab, called PR_b, has been introduced to the polymeric vesicle structure in order to provide selectivity for the alpha(5)beta(1) integrin, an adhesion molecule over-expressed on the cell surface of colon cancer cells. Following self assembly of amphiphilic block copolymers in water to form the polymersomes, the vesicle surface is covalently decorated with the PR_b peptide utilizing "click" chemistry. The polymers and peptide-functionalized polymeric nanoparticles have been characterized with a variety of experimental techniques such as SEC, NMR, MALDI, TEM, and DLS. The PR_b functionalized polymersomes have been further characterized with in vitro studies and our flow cytometry and confocal imaging data will be discussed. Our studies demonstrate that the peptide-functionalized polymersomes show superior targeting and internalization to CT26 colon cancer cells compared to non-functionalized polymersomes, thus making them a promising agent for targeted drug delivery.