A Redox-responsive Prodrug Nanogel of TLR7/8 Agonist for Improved Cancer Immunotherapy  

作　　者：Kai-Shuo Wang Yu-Feng Jin Qi-Song Tong Yong-Cong Huang Zhen-Lin Gao Sui-Juan Zheng Jing-Yang Zhang Jun Wang Jin-Zhi Du 

机构地区：[1]School of Medicine,South China University of Technology,Guangzhou,510006,China [2]School of Biomedical Sciences and Engineering,Guangzhou International Campus,South China University of Technology,Guangzhou,511442,China [3]National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou,510006,China [4]Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,and Guangdong Provincial Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou,510006,China

出　　处：《Chinese Journal of Polymer Science》2023年第1期32-39,共8页高分子科学（英文版）

基　　金：the National Natural Science Foundation of China(Nos.51922043,52173122 and 31771091);Guangdong Provincial Program(No.2017GC010304);Science and Technology Planning Project of Ganzhou(No.202101074816);Fundamental Research Funds for Central Universities.

摘　　要：The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.

关 键 词：NANOGEL Drug delivery Tumor-associated macrophage Macrophage repolarization Cancer immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤]