Dual-responsive Nanovaccine for Cytosolic Delivery of Antigens to Boost Cellular Immune Responses and Cancer Immunotherapy.

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years.A major challenge of cancer vaccine is to target cytosols of dendritic cells(DCs)in the lymph nodes(LNs)to enhance efficiency of antigen cross-presentation,which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells.Here,we address this issue by conjugating ovalbumin(OVA)to PEG-PCL using disulfide bond(-ss-),and the degradable pH-responsive polymer-PEI-PCL as delivery carrier.In addition,the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs.Subsequently,CpG ODN1826,a TLR-9 agonist,was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine.Importantly,the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs,meanwhile,OVA was modified to the surface of mixed micelles via disulfide bonds(-ss-)for promotion efficiency of antigen cross-presentation.More surprisingly,combination of tumor vaccine with anti-PD-1,the therapy of ectopic melanoma(B16-OVA)and lung metastasis melanoma(B16-OVA)is excellent therapeutic effect.Taken together,our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.