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A'three musketeers'tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy

查看全文 作　　者：Wenxi [1,2]Li;Lisi [1,2]Xie;Yi [3]Ju;Zhan [1,2]Zhang;Bei [1,2]Li;Jie [1,2]Li;Wei [1,2]Sang;Guohao [1,2]Wang;Hao [1,2]Tian;Yunlu [1,2]Dai 高影响力作者 机构地区：[1]Cancer Centre and Institute of Translational Medicine,Faculty of Health Sciences,University of Macao,Macao 999078,China;[2]MOE Frontiers Science Center for Precision Oncology,University of Macao,Macao 999078,China;[3]School of Health and Biomedical Sciences,RMIT University,Bundoora,Victoria 3083,Australia高影响力机构 出　　处：《Nano Research》索引2022年第15卷第4期,共13页高影响力期刊 基　　金：This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.32171318 and 32101069);the Faculty of Health Sciences,University of Macao,the Start-up Research Grant(SRG)of University of Macao(No.SRG2018-00130-FHS);the Science and Technology Development Fund,Macao SAR(Nos.0109/2018/A3,0011/2019/AKP,0113/2019/A2,and 0103/2021/A);Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004);We appreciate the assistance and support from the Proteomics,Metabolomics and Drug Development Core,Animal Research Core,and Biological Imaging and Stem Cell Core in the Faculty of Health Sciences,University of Macao. 摘　　要：Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune response.Unfortunately,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect.In this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor cells.IDO-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of IDO-1.To turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade.Together,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy. 关 键 词：interferon-γ(IFN-γ) anti-PD-L1(aPD-L1) IDO-1 inhibitor(NLG919) NEUTRALIZATION tumoricidal positive anti-tumor feedback loop
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