文献类型：期刊文献

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

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

机构：[1]Department of Pharmacy,Naval Medical University,Shanghai 200433,China;[2]Changhai Clinical Research Unit,Shanghai Changhai Hospital,Naval Medical University,Shanghai 200433,China;[3]Institute of Translational Medicine,Shanghai University,Shanghai 200444,China;[4]Department of Pharmacy,Shanghai Eastern Hepatobiliary Surgery Hospital,Naval Medical University,Shanghai 200433,China;[5]Department of Oncology,Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai 200434,China;[6]Unit for Drug and Instrument Supervision and Inspection of Wuxi Joint Logistic Support Center,Nanjing 210000,China;[7]Key Laboratory for Ultrafine Materials of Ministry of Education,Engineering Research Center for Biomedical Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China;[8]Department of Gastroenterology,Shanghai Changhai Hospital,Naval Medical University,Shanghai 200433,China;[9]Department of Neurology,Changzheng Hospital,Naval Medical University,Shanghai 200003,China;[10]Department of Biomaterial,College of Life Sciences,Mudanjiang Medical University,Mudanjiang 157011,China;[11]Department of Laboratory Medicine,Hongqi Hospital,Mudanjiang Medical College,Mudanjiang 157011,China;[12]Centre for Biomedical Technologies,Queensland University of Technology,Brisbane QLD 4000,Australia mWenzhou Institute of Shanghai University,Wenzhou 325000,China

年份：2022

卷号：12

期号：7

起止页码：3124

中文期刊名：Acta Pharmaceutica Sinica B

外文期刊名：药学学报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2021_2022】；PubMed;

基金：supported by the National Natural Science Foundation of China(82072051,81771964,81803450,51973060,81772317,81871753);National Key R&D Program of China(2018YFE0201500);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);by the Research Project of Shanghai Fourth People’s Hospital(sykyqd 00701&00702,China)。

语种：英文

中文关键词：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-Au NPs).PEG-Au NPs 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 m RFP-GFP-LC3 assay and analyzing the autophagy-related proteins(LC3,beclin1 and P62),PEGAu NPs induced autophagic flux inhibition in TAMs,which is attributed to the PEG-Au NPs induced lysosome alkalization and membrane permeabilization.Besides,TAMs were prone to polarize towards M2phenotype following autophagy activation,whereas inhibition of autophagic flux could reduce the M2polarization of TAMs.Our results revealed a mechanism underlying PEG-Au NPs induced antitumor immunotherapy,where PEG-Au NPs 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.