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

文献类型：期刊论文

作者Gao, Ang1,3; Chen, Binfan1,3; Gao, Jing1,3; Zhou, Fengqi1,3; Saeed, Madiha1,3; Hou, Bo1,3; Li, Yaping1,2,3; Yu, Haijun1,2,3
刊名NANO LETTERS
出版日期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
DOI10.1021/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.
WOS关键词DELIVERY
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研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:000507151600046
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/282491]  
专题新药研究国家重点实验室
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.

入库方式： OAI收割

来源：上海药物研究所

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