In situ vaccination and gene-medeiated PD-L1 blockade for enhanced tumor immunotherapy

作     者：Yingying Hu Lin Lin Zhaopei Guo Jie Chen Atsushi Maruyama Huayu Tian Xuesi Chen Yingying Hu;Lin Lin;Zhaopei Guo;Jie Chen;Atsushi Maruyama;Huayu Tian;Xuesi Chen

作者机构：Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of ChinaHefei 230026China Jilin Biomedical Polymers Engineering LaboratoryChangchun 130022China Department of Life Science and TechnologyTokyo Institute of TechnologyNagatsutaMidoriYokohama 226-8501Japan 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2021年第32卷第5期

页      面：1770-1774页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 0702[理学-物理学] 

基　　金：The authors are thankful to the National Natural Science Foundation of China(Nos.51925305,51803210,51520105004,51873208,51973217 and 51833010) Jilin province science and technology development program(Nos.20200201075JC,20180414027GH) National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2018ZX09711003-012) 

主　　题：In situ vaccination CpG PD-L1 Immu notherapy Gene therapy 

摘      要：Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side ***,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene *** worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa *** steps could be finished within 30 *** simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined *** addition,the pH responsive delivery system reduced the side effects triggered by anti-PD *** facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.