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

doi:10.1002/adma.202102668

	Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer
	Zhou, Fengqi 1,2,3; Gao, Jing 2,3,4; Tang, Yang 4; Zou, Zhifeng 1,2,3; Jiao, Shi 5; Zhou, Zhaocai 5; Xu, Huixiong 4; Xu, Zhi Ping 6; Yu, Haijun 2,3; Xu, Zhiai 1
刊名	ADVANCED MATERIALS
	2021-08-31
页码	12
关键词	antigen presentation autophagy inhibition immune resistance immunotherapy prodrug nanovesicles
ISSN号	0935-9648
DOI	10.1002/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.
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关键词	AUTOPHAGY ; CELLS ; IMMUNOTHERAPY ; PROGRESSION ; INNATE ; TUMORS
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:000691431100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297687]
专题	中国科学院上海药物研究所
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.