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Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy

文献类型：期刊论文

作者Li, Tianliang2,3; Song, Rundi3; Sun, Fang3; Saeed, Madiha3; Guo, Xiaozhen3; Ye, Jiayi3; Chen, Fangmin3; Hou, Bo3; Zhu, Qiurong3; Wang, Yingjie3
刊名NANO TODAY
出版日期2022-04-01
卷号43页码:12
关键词Immune cascade Tumor-associated macrophages Magnetic nanocomplexes M1 polarization Stimulator of interferon genes
ISSN号1748-0132
DOI10.1016/j.nantod.2022.101400
通讯作者Yu, Haijun(hjyu@simm.ac.cn)
英文摘要Insufficient tumor-infiltration of the cytotoxic T lymphocytes (CTLs) and immunosuppressive tumor mi-croenvironment (ITM) severely hinder T cell-based cancer immunotherapy. In this study, we developed bioinspired magnetic nanocomplexes (m-PUNCs) to boost antitumor immunogenicity through amplifying stimulator of interferon genes (STING)-regulated immune cascade of tumor-associated macrophages (TAMs). m-PUNCs were engineered by integrating ultrasmall iron oxide nanoparticles (UIONPs), tumor acidity-ionizable of poly(ethylene glycol)-block-poly(2-(hexamethyleneimino)) ethyl methacrylate (PHMA) diblock copolymer, and red blood cell membrane into a single nanoplatform. The resultant m-PUNCs specifically accumulated at the tumor site via passive targeting effect, which were subsequently phago-cytized with TAMs. The UIONPs moiety efficiently relieved the ITM by repolarizing TAMs into M1-pheno-type, while PHMA activated the STING pathway and stimulated type-I interferon (e.g., IFN-beta) secretion in TAMs. Consequently, IFN-beta attracted the conventional type I dendritic cells for priming the tumor-specific CTLs. In combination with immune checkpoint blockade therapy with the antibody against programmed death ligand 1, m-PUNCs remarkably inhibited tumor growth and prolonged the survival of both melanoma and breast tumor-bearing mouse model. This study demonstrated the immune cascade of magnetic na-nocomplexes-mediated TAM repolarization and subsequent STING activation, which might provide novel insights for potentiating cancer immunotherapy. (c) 2022 Elsevier Ltd. All rights reserved.
WOS关键词SUPPRESSOR-CELLS ; IMMUNE PRIVILEGE ; T-CELLS ; POLARIZATION ; BLOCKADE ; IL-4
资助项目National Natural Science Foundation of China[32050410287] ; National Natural Science Foundation of China[52111530092] ; National Natural Science Foundation of China[51873228] ; International Cooperation Project of Science and Technology Commission of Shanghai Municipality[20430711800] ; China Postdoctoral Science Foundation[2019M661667] ; Shanghai Post-Doctoral Excellence Program[2019116] ; Open Funds of State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, CAS[SIMM2105KF-12]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000776773400002
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/299761]  
专题新药研究国家重点实验室
通讯作者Yu, Haijun
作者单位1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
2.Tongji Univ, Tongji Univ Canc Ctr, Shanghai Peoples Hosp 10, Sch Med,Dept Med Ultrasound, Shanghai 200072, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
4.Guizhou Med Univ, Guizhou Prov Engn Technol Res Ctr Chem Drug R&D, Guiyang 550025, Peoples R China
5.Fudan Univ, Zhongshan Hosp, Dept Ultrasound, Shanghai 200032, Peoples R China
推荐引用方式
GB/T 7714		 Li, Tianliang,Song, Rundi,Sun, Fang,et al. Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy[J]. NANO TODAY,2022,43:12.
APA Li, Tianliang.,Song, Rundi.,Sun, Fang.,Saeed, Madiha.,Guo, Xiaozhen.,...&Yu, Haijun.(2022).Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy.NANO TODAY,43,12.
MLA Li, Tianliang,et al."Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy".NANO TODAY 43(2022):12.

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来源：上海药物研究所

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