Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy

作者全名："Wang, Mengna; Deng, Siyu; Cao, Yijia; Zhou, Hang; Wei, Wei; Yu, Kexiao; Cao, Youde; Liang, Bing"

作者地址："[Wang, Mengna; Deng, Siyu; Wei, Wei; Cao, Youde; Liang, Bing] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China; [Cao, Yijia] Chongqing Med Univ, Univ Town Hosp, Dept Digest, Chongqing 401331, Peoples R China; [Zhou, Hang] Chongqing Med Univ, Inst Ultrasound Imaging, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Zhou, Hang] Chongqing Med Univ, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Yu, Kexiao] Chongqing Tradit Chinese Med Hosp, Dept Orthoped, 6 Panxi Seventh Branch Rd, Chongqing 400021, Peoples R China; [Cao, Youde; Liang, Bing] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Cao, Youde; Liang, Bing] Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, 1 Youyi Rd, Yuzhong Dist, Chongqing 400042, Peoples R China; [Cao, Youde; Liang, Bing] Chongqing Med Univ, Coll Basic Med, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Yu, KX (通讯作者)，Chongqing Tradit Chinese Med Hosp, Dept Orthoped, 6 Panxi Seventh Branch Rd, Chongqing 400021, Peoples R China.; Cao, YD; Liang, B (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MATERIALS TODAY BIO

ESI学科分类：　

WOS号：WOS:000867665200007

JCR分区：Q1

影响因子：8.2

年份：2022

卷号：16

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Magnetothermal; Liquid -solid transformation; Immunogenic cell death; Free radicals; CTLA4 checkpoint blockade

摘要："The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malig-nant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metas-tasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,20-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen -irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immuno-genicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was ob-tained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release."

基金机构：National Natural Science Foundation of China [82102909]; China Postdoctoral Science Foundation [2021M693754]; Chongqing Special Postdoctoral Science Foundation [2021XM2023]

基金资助正文："We acknowledge financial support from the project of the National Natural Science Foundation of China (No. 82102909) , China Postdoctoral Science Foundation (2021M693754) , and Chongqing Special Postdoctoral Science Foundation (2021XM2023) ."