文献类型：期刊文献

英文题名：Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization

作者：Zhang, Siyue[1,2,3,6];Xie, Fangyuan[1,4];Li, Kaichun[5];Zhang, He[1];Yin, You[9];Yu, Yuan[1];Lu, Guangzhao[1];Zhang, Shihao[7];Wei, Yan[3];Xu, Ke[3];Wu, Yan[10];Jin, Hong[11];Xiao, Lan[12];Bao, Leilei[4];Xu, Can[8];Li, Yulin[7,13];Lu, Ying[1];Gao, Jie[2,3]

机构：[1]Naval Med Univ, Dept Pharm, Shanghai 200433, Peoples R China;[2]Naval Med Univ, Shanghai Changhai Hosp, Changhai Clin Res Unit, Shanghai 200433, Peoples R China;[3]Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China;[4]Naval Med Univ, Shanghai Eastern Hepatobiliary Surg Hosp, Dept Pharm, Shanghai 200433, Peoples R China;[5]Tongji Univ, Shanghai Peoples Hosp 4, Sch Med, Dept Oncol, Shanghai 200434, Peoples R China;[6]Wuxi Joint Logist Support Ctr, Unit Drug & Instrument Supervis & Inspect, Nanjing 210000, Jiangsu, Peoples R China;[7]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Sch Mat Sci & Engn, Key Lab Ultrafine Mat,Minist Educ, Shanghai 200237, Peoples R China;[8]Naval Med Univ, Shanghai Changhai Hosp, Dept Gastroenterol, Shanghai 200433, Peoples R China;[9]Naval Med Univ, Changzheng Hosp, Dept Neurol, Shanghai 200003, Peoples R China;[10]Mudanjiang Med Univ, Coll Life Sci, Dept Biomat, Mudanjiang 157011, Peoples R China;[11]Mudanjiang Med Coll, Hongqi Hosp, Dept Lab Med, Mudanjiang 157011, Peoples R China;[12]Queensland Univ Technol, Ctr Biomed Technol, Brisbane, Qld 4000, Australia;[13]Wenzhou Inst Shanghai Univ, Wenzhou 325000, Peoples R China

年份：2022

卷号：12

期号：7

起止页码：3124

外文期刊名：ACTA PHARMACEUTICA SINICA B

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000827613600011)】；

基金：This work was supported by the National Natural Science Foun- dation of China (82072051, 81771964, 81803450, 51973060, 81772317, 81871753) and National Key R&D Program of China (2018YFE0201500) . This work was funded by the Special Project of Clinical Research of Health Industry of Shanghai Municipal Health Commission (No. 201940178, China) , by the Scientific Research Project of Hongkou District Health Committee of Shanghai (No. 2002-17, China) , by the Clinical Research Project of Wu Jieping Medical Foundation (No. 320.6750.2020-18-2, China) , and by the Research Project of Shanghai Fourth People?s Hospital (sykyqd 00701 & 00702, China) .

语种：英文

外文关键词：Macrophage polarization; Tumor-associated macrophages; Nanomaterials; Autophagy flux; Lysosomal damage; Gold nanoparticles; M2 macrophage; Cancer therapy

摘要：Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.