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Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer

文献类型：期刊论文

作者Zhou, Fengqi1,2,3; Gao, Jing2,3,4; Tang, Yang4; Zou, Zhifeng1,2,3; Jiao, Shi5; Zhou, Zhaocai5; Xu, Huixiong4; Xu, Zhi Ping6; Yu, Haijun2,3; Xu, Zhiai1
刊名ADVANCED MATERIALS
出版日期2021-08-31
页码12
关键词antigen presentation autophagy inhibition immune resistance immunotherapy prodrug nanovesicles
ISSN号0935-9648
DOI10.1002/adma.202102668
通讯作者Yu, Haijun(hjyu@simm.ac.cn) ; Xu, Zhiai(zaxu@chem.ecnu.edu.cn)
英文摘要Immune evasion is the major obstacle for T-cell-based cancer immunotherapy. The insufficient expression of the tumor-rejection antigen causes the intrinsic immune resistance and high expression of programmed death ligand 1 (PD-L1) induced by interferon gamma (IFN-gamma), which accounts for the inducible immune resistance. To deal with both the intrinsic and inducible immune resistance of cancer, a multifunctional prodrug nanovesicle is sequentially developed. It is first sorted out that doxycycline (Doxy) efficiently inhibits autophagy of the tumor cells, and increases the surface level of major histocompatibility complex class I (MHC-I). Then, chameleon-inspired prodrug nanovesicles are engineered for tumor-targeted delivery of Doxy. The prodrug nanovesicles integrating a sheddable poly(ethylene glycol) shell and CRGDK ligand are kept stable during blood circulation, while exposing the targeting ligand in the tumor, which significantly inhibits autophagy, elicits MHC-I expression, increases tumor antigen presentation, recruits more tumor-infiltrating T lymphocytes, and suppresses FN-gamma-induced intratumoral PD-L1 expression. After a proof of concept for overcoming intrinsic and inducible immune evasion, the prodrug nanovesicles are applied to validate the efficacy of cancer immunotherapy in two tumor-bearing mouse models. This research thus provides a novel targeting strategy for reducing tumor immune resistance and potentiating tumor immunotherapy.
WOS关键词AUTOPHAGY ; CELLS ; IMMUNOTHERAPY ; PROGRESSION ; INNATE ; TUMORS
资助项目National Natural Science Foundation of China[22074043] ; National Natural Science Foundation of China[51873228] ; International Cooperation Project of Science and Technology Commission of Shanghai Municipality[20430711800] ; Youth Innovation Promotion Association of CAS[2014218] ; Fudan University[FU-SIMM-20182006] ; Shanghai Institute of Materia Medica, CAS[FU-SIMM-20182006] ; Open Funds of State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, CAS[SIMM2105KF-12] ; Open Project Program of Key Lab of Smart Drug Delivery (Ministry of Education), Department of Pharmaceutics, School of Pharmacy, Fudan Universit
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:000691431100001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/297687]  
专题新药研究国家重点实验室
通讯作者Yu, Haijun; Xu, Zhiai
作者单位1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
4.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Canc Ctr, Shanghai 200072, Peoples R China
5.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China
6.Univ Queensland, Australian Inst Bioengn & Nanotechnol, St Lucia, Qld 4072, Australia
推荐引用方式
GB/T 7714		 Zhou, Fengqi,Gao, Jing,Tang, Yang,et al. Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer[J]. ADVANCED MATERIALS,2021:12.
APA Zhou, Fengqi.,Gao, Jing.,Tang, Yang.,Zou, Zhifeng.,Jiao, Shi.,...&Xu, Zhiai.(2021).Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer.ADVANCED MATERIALS,12.
MLA Zhou, Fengqi,et al."Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer".ADVANCED MATERIALS (2021):12.

入库方式： OAI收割

来源：上海药物研究所

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