(313c) Polymersomes Functionalized with the PR_b Fibronectin-Mimetic Peptide Using Click Chemistry Promote Targeted Drug Delivery to Cancer Cells

Polymersomes, high molecular weight analogues to liposomes, have been proposed as a promising drug encapsulation and delivery system, exhibiting high stability and sufficient stealth macrophage evasion. We synthesized amphiphilic block copolymers?poly(ethylene oxide)-b-poly(1,2-butadiene)?that self-assemble to form polymersomes, which were further functionalized with targeting ligands using azide-alkyne "click" chemistry. Peptide targeting ligands, PR_b (KSSPHSRN(SG)₅RGDSP) and GRGDSP were conjugated onto preformed polymersomes at a range of surface concentrations, and the efficacy of drug delivery to colon and breast cancer cells of these polymersomes was compared. These peptide ligands mimic the cell adhesion domain of native fibronectin protein. PR_b, a peptide recently designed by our group, has been shown to bind with high specificity to the α₅β₁ integrin that is overexpressed on the surface of colon and breast cancer cells. Drug delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent markers or the chemotherapeutic, doxorubicin, was quantitatively assessed and compared. In addition the cell binding and internalization of fluorescently labeled polymersomes was imaged using confocal microscopy. PR_b functionalized polymersomes were shown to outperform both GRGDSP functionalized and non-functionalized polymersomes in drug delivery to both colon and breast cancer cells, and are highlighted as a promising drug delivery system for future study.