Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment

doi:10.1002/adma.201803001

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	Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment
	Feng, Bing 2,3,4; Zhou, Fangyuan 3,4; Hou, Bo 3,4; Wang, Dangge 2,3,4; Wang, Tingting 2,3,4; Fu, Yuanlei 3,4; Ma, Yuting 1,5,6; Yu, Haijun2,3,4 ; Li, Yaping2,3,4
刊名	ADVANCED MATERIALS
	2018-09-20
卷号	30 期号:38
关键词	immune tumor microenvironment immunogenic cell death immunotherapy prodrug nanoparticles stimuli-activation
ISSN号	0935-9648
DOI	10.1002/adma.201803001
文献子类	Article
英文摘要	Checkpoint blockade immunotherapy is promising for clinical treatment of various malignant tumors. However, checkpoint blockade immunotherapy suffers from a low response rate due to insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (ITM). In this study, a tumor-microenvironment-activatable binary cooperative prodrug nanoparticle (BCPN) is rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. BCPN is purely constructed from a tumor acidity and reduction dual-responsive oxaliplatin (OXA) prodrug for triggering immunogenic cell death (ICD) and eliciting antitumor immunity, and a reduction-activatable homodimer of NLG919 for inactivating indoleamine 2,3-dioxygenase 1, which is a key regulator for ITM. Upon tumor-acidity-triggered cleavage of the poly(ethylene glycol) shell, PN shows negative to positive charge switch for enhanced tumor accumulation and deep penetration. OXA and NLG919 are then activated in the tumor cells via glutathione-mediated reduction. It is demonstrate that activated OXA promotes intratumoral accumulation of cytotoxic T lymphocytes by triggering ICD of cancer cells. Meanwhile, NLG919 downregulates IDO-1-mediated immunosuppression and suppresses regulatory T cells. Most importantly, PN shows much higher efficiency than free OXA or the combination of free OXA and NLG919 to regress tumor growth and prevent metastasis of mouse models of both breast and colorectal cancer.
资助项目	National Natural Science Foundation of China[31671024] ; National Natural Science Foundation of China[31622025] ; National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81671630] ; National Natural Science Foundation of China[81722037]
WOS关键词	CANCER-THERAPY ; IMMUNOGENIC CHEMOTHERAPY ; CHECKPOINT BLOCKADE ; T-CELLS ; IMMUNOCHEMOTHERAPY ; RESISTANCE ; INHIBITORS ; RESPONSES ; ONCOLOGY ; DELIVERY
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000444671900024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279576]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yu, Haijun; Li, Yaping
作者单位	1.Suzhou Inst Syst Med, Suzhou 215123, Jiangsu, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China; 5.Peking Union Med Coll, Beijing 100005, Peoples R China; 6.Chinese Acad Med Sci, Ctr Syst Med, Inst Basic Med Sci, Beijing 100005, Peoples R China;
推荐引用方式 GB/T 7714	Feng, Bing,Zhou, Fangyuan,Hou, Bo,et al. Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment[J]. ADVANCED MATERIALS,2018,30(38).
APA	Feng, Bing.,Zhou, Fangyuan.,Hou, Bo.,Wang, Dangge.,Wang, Tingting.,...&Li, Yaping.(2018).Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment.ADVANCED MATERIALS,30(38).
MLA	Feng, Bing,et al."Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment".ADVANCED MATERIALS 30.38(2018).