| Self-assemblies of amphiphilic block copolymers are helping to define an emerging, and rapidly metamorphosing, class of novel environmentally sensitive drug delivery systems. This thesis explores the controlled release and drug delivery potential of degradable, diblock copolymer vesicles, polymersomes. This is a systematic presentation of initial physical-chemical characterization of spontaneously self-assembled bilayer vesicles; followed by details on passive uptake of these neutral carriers by cancer cells, 'macro'-surfactant generation and escape from endolysosomal barriers, and intracellular delivery of cytotoxic drugs to their intracellular targets. Since the final assessment of all drug delivery vehicles is its vivo efficacy, we also show promising initial combination therapy of drug-loaded polymersomes in xenograft model of breast cancer. This in vivo efficacy was contingent upon prolonged circulation and passive residence in the leaky tumor environment. In the end, with an effort towards active tumor targeting, we isolated anti-CD47 ligands to selectively target and trigger apoptosis in selective CD47 expressing epithelial cancers. |
