Effective intracellular delivery and Th1 immune response induced by ovalbumin loaded in pH-responsive polyphosphazene polymersomes

Abstract A polymersome system for delivering protein antigen ovalbumin (OVA) based on amphiphilic polyphosphazene grafting with N,N-diisopropylethylenediamine (DPA) and poly(ethylene glycol) (PEG) groups (poly[(DPA) m (PEG) n phosphazene], PEDP) was designed and constructed. The 200-240 nm-size OVA-loaded polymersomes displayed high stability at physiological pH, slow internalization through clathrin-mediated endocytosis pathway, and then a pH-triggered sustained OVA release in acidic environment, leading to extensive antigen access to cytosol. Prime-boost vaccine kept high antibody titers for 8 weeks and the subcutaneous vaccine of OVA polymersomes biased the immune response towards a type 1 T helper (Th1) response. Animal experiment results showed that the antigen-specific prophylactic vaccination by PEDP polymersomes delivery was much more rapid and efficient in depressing tumor growth and progress when compared with the therapeutic vaccination. These results suggested that PEDP-based polymersomes are very promising in controlled cytosolic delivery of protein antigens, and enhanced Th1 specific immune response.