Bio-membrane adhesive poly(choline phosphate l-glutamate)-based nanoparticles as vaccine delivery systems for cancer immunotherapy

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Vaccination is a widely used efficient method to prevent or to treat a series of diseases. However, current widely-used vaccines usually could not induce strong cellular immunity, which limits their clinical applications in tumor immunotherapy. Therefore, to design and develop effective vaccine delivery systems to induce strong antigen-specific immune response has attracted more and more attention. In this work, a novel bio-membrane adhesive biodegradable cationic polymer poly(choline phosphate l-glutamate) (pCPGlu) was synthesized and evaluated as a vaccine carrier to deliver model antigen protein ovalbumin (OVA). To prepare the pCPGlu, a biodegradable poly(l-glutamate) was functionalized with a choline phosphate (CP) group which could strongly adsorb to cell membranes and then rapidly enter cells. Then, cationic nanoparticles pCPGlu/OVA were formed via electrostatic attraction between the polycationic pCPGlu and negatively charged OVA. The pCPGlu/OVA nanoparticles were efficiently internalized by immature dendritic cells and escaped from lysosomes into the cytoplasm to induce cross-presentation. As a result, the pCPGlu/OVA nanoparticles could provide adequate initial and long-term antigen exposure to stimulate immune response. After subcutaneously immunized with the pCPGlu/OVA nanoparticles in C57BL/6 mice, the antigen-specific immune responses were investigated. The results indicate that, the pCPGlu/OVA nanoparticles could induce more potent antigen-specific humoral and cellular immune response with significantly higher level of activation of dendritic cells, OVA-specific IgG antibodies, splenocytes proliferation, cytokine secretion, and activation of effector memory T cells. Moreover, subcutaneous administration of the pCPGlu/OVA nanoparticles to the E.G7-OVA tumor-bearing mice significantly increased the amount of cytotoxic T lymphocytes, inhibited the tumor growth, and prolonged the mice survival. Taken together, the cationic cell membrane adhesive pCPGlu could be a safe and potent antigen delivery system for efficient cancer immunotherapy.