Dual-responsive nanovaccine for cytosolic delivery of antigens to boost cellular immune responses and cancer immunotherapy  

作　　者：Yang Sui Ji Li Jiqiang Qu Ting Fang Hongyan Zhang Jian Zhang Zheran Wang Mingyu Xia Yinghui Dai Dongkai Wang 

机构地区：[1]Department of Pharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Department of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang 110016,China [3]Department of Mathematics and Statistics,Auburn University,Auburn,AL 36849,USA [4]School of Life Science and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China [5]School of Pharmacy,China Medical University,Shenyang 110122,China [6]School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第4期583-595,共13页亚洲药物制剂科学（英文）

摘　　要：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 ODN_(1826),a TLR-9 agonist,was further introduced into a mixed micelle of 30nm or less as a unique tumor vaccine.Importantly,the results demonstrated the mixed micelles with 1:1mol 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.

关 键 词：REDUCIBLE Nanoparticles Vaccine CROSS-PRESENTATION Immunotherapy Immune checkpoint blockade 

分 类 号：R730.51[医药卫生—肿瘤]