Sheddable Prodrug Vesicles Combating Adaptive Immune Resistance for Improved Photodynamic Immunotherapy of Cancer

doi:10.1021/acs.nanolett.9b04012

	Sheddable Prodrug Vesicles Combating Adaptive Immune Resistance for Improved Photodynamic Immunotherapy of Cancer
	Gao, Ang 1,3; Chen, Binfan 1,3; Gao, Jing 1,3; Zhou, Fengqi 1,3; Saeed, Madiha 1,3; Hou, Bo 1,3; Li, Yaping 1,2,3; Yu, Haijun 1,2,3
刊名	NANO LETTERS
	2020
卷号	20 期号:1 页码:353-362
关键词	Cancer immunotherapy photodynamic therapy adaptive immune resistance indoleamine 2,3-dioxygenase 1 prodrug vesicles
ISSN号	1530-6984
DOI	10.1021/acs.nanolett.9b04012
通讯作者	Li, Yaping(ypli@simm.ac.cn) ; Yu, Haijun(hjyu@simm.ac.cn)
英文摘要	Photodynamic therapy (PDT) capable of eliciting a robust antitumor immune response has been considered an attractive therapeutic approach. However, adaptive immune resistance in PDT underlines the need to develop alternative strategies. The exquisite power of checkpoint blockade can be harnessed to reinvigorate antitumor immune response. Here, we demonstrate that PDT-triggered adaptive immune resistance can be overcome by inactivating indoleamine 2,3-dioxygenase 1 (IDO-1). We rationally designed a tumor-microenvironment-sheddable prodrug vesicle by integrating a PEGylated photosensitizer (PS) and a reduction-sensitive prodrug of IDO-1 inhibitor. The prodrug vesicles were inert during the blood circulation, whereas they specifically accumulated and penetrated at the tumor site through matrix metalloproteinase-2 (MMP-2)-mediated cleavage of the PEG corona to achieve fluorescence-imaging-guided photodynamic therapy (PDT). Compared to PDT alone, the prodrug-vesicle-mediated combination immunotherapy provoked augmented antitumor immunity to eradicate the tumor in both CT26 colorectal and 4T1 breast immunocompetent mouse models. The prodrug vesicles dramatically suppressed tumor reoccurrence, particularly in overexpressing IDO-1 tumor models, i.e., CT26. This study might provide novel insight into the development of new nanomedicine to enhance the efficacy of photodynamic immunotherapy while addressing the adaptive immune resistance.
资助项目	National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[31671024] ; National Natural Science Foundation of China[31622025] ; National Natural Science Foundation of China[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; Youth Innovation Promotion Association of Chinese Academy of Sciences[2014218] ; Fudan University[FU-SIMM-20182006] ; Shanghai Institute of Materia Medica[FU-SIMM-20182006]
WOS关键词	DELIVERY
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000507151600046
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282491]
专题	中国科学院上海药物研究所
通讯作者	Li, Yaping; Yu, Haijun
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China 3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Gao, Ang,Chen, Binfan,Gao, Jing,et al. Sheddable Prodrug Vesicles Combating Adaptive Immune Resistance for Improved Photodynamic Immunotherapy of Cancer[J]. NANO LETTERS,2020,20(1):353-362.
APA	Gao, Ang.,Chen, Binfan.,Gao, Jing.,Zhou, Fengqi.,Saeed, Madiha.,...&Yu, Haijun.(2020).Sheddable Prodrug Vesicles Combating Adaptive Immune Resistance for Improved Photodynamic Immunotherapy of Cancer.NANO LETTERS,20(1),353-362.
MLA	Gao, Ang,et al."Sheddable Prodrug Vesicles Combating Adaptive Immune Resistance for Improved Photodynamic Immunotherapy of Cancer".NANO LETTERS 20.1(2020):353-362.