Endosomolytic Biomaterial Vaccines for Cancer Therapy

Abstract

Stimuli-responsive biomaterials are useful for a variety of therapeutic applications because they function in concert with naturally occurring biological processes. This dissertation is focused on applications of a pH-responsive biomaterial known as the “Virus-Inspired Polymer for Endosomal Release,” or VIPER. VIPER is a cationic polymer-peptide conjugate designed for intracellular delivery of nucleic acids. It self-assembles into nanoparticles at neutral pH and disassembles at acidic pH to expose melittin, a membrane-lytic peptide. Using this pH-responsive lytic mechanism, VIPER disrupts endosome membranes after cellular uptake into acidic endosomal compartments, delivering its cargo to the cytosol in a virus-like fashion. We aim to use VIPER as a platform technology for delivery of cancer vaccines. Because the bioactivities of tumor antigens and vaccine adjuvants may be augmented by VIPER’s membrane-lytic properties, VIPER-mediated delivery of vaccine components to immune cell populations may potentiate anticancer immune responses.