Poly(amido Amine)and Polymer Dots As Vaccine Delivery Systems For Cancer Immunotherapy

Vaccination are safe and effective methods for preventing and treating various diseases.However,traditional vaccines usually cause humoral immune responses in the body and do not lead to effective cellular immune responses for cancer therapy.Therefore,in order to enhance the cellular immune response of vaccines,numerous vaccine delivery systems have been developed,especially cationic nanoparticle for vaccine delivery system.Cationic polymer dots（PDs）have been widely used for biomedical imaging and drug delivery due to their excellent photoluminescence,small size and abundant positive charge.In this study,in order to achieve effective treatment of cancer,polyethyleneimine(PEI₆₀₀,M.W.600,99%)modified redox-responsive hyperbranched poly（amido amine）(PAA-PEI₆₀₀)and partially carbonized PAA-PEI₆₀₀PDs were designed and prepared as vaccine carriers to deliver the model antigen protein ovalbumin（OVA）.First,the physical chemistry characterization,cytotoxicity,cellular uptake and antigen load and release detection of PAA-PEI₆₀₀00 and PDs also with the PAA-PEI₆₀₀/OVA and PDs/OVA nanoparticles(formed by PAA-PEI₆₀₀00 and PDs with OVA through electrostatic adsorption respectively)were tested in vitro.The results suggest that both cationic materials have redox responsiveness.Further,the both cationic materials have good cell safety,cellular uptake and load and release capabilities within the concentration range used in this study.Then,OVA-specific immune responses induced by PAA-PEI₆₀₀/OVA and PDs/OVA nanoparticles were evaluated in vivo.The results suggest that the PAA-PEI₆₀₀/OVA and PDs/OVA nanoparticles significantly enhanced OVA-specific immune responses when compared to OVA alone.Further,PDs/OVA nanoparticles induced more potent OVA-specific cellular immune responses,including higher levels of the OVA-specific IgG 2a/IgG 1 antibody ratio,splenocyte proliferation activity,secretion of IL-12 and IFN-γcytokines,maturation of dendritic cells,antigen cross-presentation,number of effector memory CD4⁺T cells and CD8⁺T cells as well as cytotoxic T lymphocytes（CTL）than PAA-PEI₆₀₀/OVA nanoparticles did.Moreover,subcutaneously injected PDs/OVA nanoparticles significantly inhibited tumor growth of the mice bearing E.G7-OVA tumor and extended mice survival.All the results show that immunization with PDs/OVA nanoparticles elicited more effective OVA-specific cellular immune responses.PDs could serve as promising vaccine delivery system for cancer immunotherapy.