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Breaking Tumor Immunosuppressive Network by Regulating Multiple Nodes with Triadic Drug Delivery Nanoparticles

文献类型：期刊论文

作者Yan, Wenlu4,5,6,7; Li, Yu6,7; Zou, Yiting2; Zhu, Runqi5,6,7; Wu, Ting1,6,7; Sun, Xujie5,6,7; Yuan, Wenhui5,6,7; Lang, Tianqun6,7; Yin, Qi4,5,6,7; Li, Yaping2,3,4,5,6,7
刊名ACS NANO
出版日期2023-09-10
卷号17期号:18页码:17826-17844
ISSN号1936-0851
关键词triple-negative breast cancer antitumor immunity tumor-associated macrophages myeloid-derived suppressorcells immune network nanoparticle
DOI10.1021/acsnano.3c03387
通讯作者Lang, Tianqun(langtq@lglab.ac.cn) ; Yin, Qi(qyin@simm.ac.cn) ; Li, Yaping(ypli@simm.ac.cn)
英文摘要Inside the tumor microenvironment, a complicated immunosuppressive network is constituted by tumor cells and suppressive immune cells as its nodes, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells, which have mutual promotion on each other and superimposed inhibition on natural killer (NK) cells and cytotoxic T cells. Breaking the whole balance of this web is critical to tumor immunotherapy since modulation on a single node may be diluted by other factors in the network. To achieve multifaceted regulation on antitumor immunity against triple-negative breast cancer, in this work, a micelle, termed BEM, co-delivering the MDSC inhibitor, entinostat (ENT), and the immune checkpoint inhibitor, BMS-1, was constructed with pH-sensitive amphiphilic poly(ss-amino ester) derivatives. Then, BEM and the scavenger receptor A (SR-A) ligand dextran sulfate ( DXS) formed a negatively charged nanoparticle (BEN). DXS detached from BEN in the weakly acidic tumor microenvironment and blocked SR-A on TAMs, reprogramming TAMs toward the M1 type. The positively charged BEM with facilitated intratumoral penetration and cellular uptake dissociated in the lysosomes, accompanied by the release of ENT and BMS-1 to suppress MDSCs and block the programmed cell death protein (PD)-1/PD-ligand 1 pathway, respectively. As a result, NK cells and CD8+ T cells in tumors were increased, as were their effector cytokines. The activated innate and adaptive antitumor immune responses suppressed the growth and metastasis of tumors and prolonged survival of 4T1 tumor-bearing mice. BEN provides a reliable approach for improving cancer immunotherapy by destroying the immunosuppression web in tumors via multinode regulation.
WOS关键词SUPPRESSOR-CELLS ; SCAVENGER RECEPTOR ; SIGNALING PATHWAYS ; CROSS-TALK ; MACROPHAGES ; IMMUNOSURVEILLANCE ; PENETRATION ; BINDING
资助项目National Key R&D Program of China[2022YFC3401404] ; National Natural Science Foundation of China[32171315] ; National Natural Science Foundation of China[31930066] ; National Natural Science Foundation of China[32130058] ; Natural Science Foundation of Shandong[ZR2019ZD25] ; Science and Technology Innovation Action Plan Sailing Plan of Shanghai[22YF1460500]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:001065448500001
源URL[http://119.78.100.183/handle/2S10ELR8/307275]  
专题新药研究国家重点实验室
通讯作者Lang, Tianqun; Yin, Qi; Li, Yaping
作者单位1.Nanjing Med Univ, Sch Pharm, Dept Pharmaceut, Nanjing 211116, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
5.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Yan, Wenlu,Li, Yu,Zou, Yiting,et al. Breaking Tumor Immunosuppressive Network by Regulating Multiple Nodes with Triadic Drug Delivery Nanoparticles[J]. ACS NANO,2023,17(18):17826-17844.
APA Yan, Wenlu.,Li, Yu.,Zou, Yiting.,Zhu, Runqi.,Wu, Ting.,...&Li, Yaping.(2023).Breaking Tumor Immunosuppressive Network by Regulating Multiple Nodes with Triadic Drug Delivery Nanoparticles.ACS NANO,17(18),17826-17844.
MLA Yan, Wenlu,et al."Breaking Tumor Immunosuppressive Network by Regulating Multiple Nodes with Triadic Drug Delivery Nanoparticles".ACS NANO 17.18(2023):17826-17844.

入库方式： OAI收割

来源：上海药物研究所

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