Reduction-sensitive nanogels for tumor vaccination

Abstract

An attractive approach to induce a strong immune response against a certain tumor antigen is targeting it to DCs with a nano-sized carrier that keeps the antigen encapsulated or associated with the particles until the carriers are internalized by DCs. Given the superior properties of nanogels as delivery systems and the responsiveness of disulfide bonds crosslinked systems, reduction sensitive nanogel delivery systems based on dextran and crosslinkers/polymers containing disulfide bonds were developed in this thesis as potential carriers for antigens. The main emphasis was on the preparation of nanogel delivery systems in which a protein antigen is reversibly conjugated to nanogels via disulfide bonds or entrapped in nanogels coated with disulfide crosslinked networks. The antigens should be stably encapsulated in the nanogels in the extracellular space, but should be released in the reducing environment inside DCs. Additionally, this thesis focusses also on obtaining a better insight into the role of the formulation of particulate delivery systems in enhancing antigen specific CD8+ T cell activation in vitro and in vivo for tumor vaccination.