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Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy

文献类型：期刊论文

作者Ye, Jiayi1,2,3; Hou, Bo2,3,4; Chen, Fangmin1,2,3; Zhang, Shunan2,3,4; Xiong, Muya1,5,6; Li, Tianliang2,3; Xu, Yechun1,5,6,7; Xu, Zhiai4; Yu, Haijun1,2,3
刊名ACTA PHARMACEUTICA SINICA B
出版日期2022-06
卷号12期号:6页码:2695-2709
ISSN号2211-3835
关键词Immunotherapy Prodrug nanoparticles Immune evasion Immunogenic cell death Tumor microenvironment
DOI10.1016/j.apsb.2021.09.021
文献子类Article
英文摘要Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
WOS关键词ACQUIRED-RESISTANCE ; INTERFERON-GAMMA ; INHIBITION ; PACLITAXEL ; CHALLENGES ; ANTIBODIES ; PROTECTS ; TUMORS ; IDO
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号WOS:000824668200007
源URL[http://119.78.100.183/handle/2S10ELR8/309340]  
专题新药研究国家重点实验室
通讯作者Yu, Haijun
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
4.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China;
5.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China;
6.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China;
7.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310013, Peoples R China
推荐引用方式
GB/T 7714		 Ye, Jiayi,Hou, Bo,Chen, Fangmin,et al. Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy[J]. ACTA PHARMACEUTICA SINICA B,2022,12(6):2695-2709.
APA Ye, Jiayi.,Hou, Bo.,Chen, Fangmin.,Zhang, Shunan.,Xiong, Muya.,...&Yu, Haijun.(2022).Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy.ACTA PHARMACEUTICA SINICA B,12(6),2695-2709.
MLA Ye, Jiayi,et al."Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy".ACTA PHARMACEUTICA SINICA B 12.6(2022):2695-2709.

入库方式： OAI收割

来源：上海药物研究所

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