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Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy

文献类型：期刊论文

作者Hou, Bo1,2,3,4; Ye, Jiayi2,3,5; Huang, Lujia2,3,5; Cheng, Wenhao2,3; Chen, Fangmin2,3,5; Zhou, Huiling1,2,3; Pan, Jiaxing2,3; Gao, Jing2,3; Lai, Yi2,3; Zhao, Yujun6,7
刊名SCIENCE ADVANCES
出版日期2024-11-15
卷号10期号:46页码:17
ISSN号2375-2548
DOI10.1126/sciadv.adq3940
英文摘要Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups. This enables covalently binding of the clickable inhibitor with PD-L1 and subsequent PD-L1 degradation. A pH-activatable nanoparticle responding to extracellular acidic pH of tumor was subsequently used to deliver the clickable PD-L1 inhibitor into extracellular tumor microenvironment for depleting PD-L1 on the surface of tumor cell and macrophage membranes in vivo. We further demonstrated that a combination of the clickable PD-L1 inhibitor with radiotherapy (RT) eradicated the established tumor by inhibiting RT-up-regulated PD-L1 in the tumor tissue. Therefore, selective PD-L1 blockade in tumors via the clickable PD-L1 inhibitor offers a versatile approach to promote cancer immunotherapy.
WOS关键词MECHANISMS ; MICROENVIRONMENT ; NANOPARTICLES ; RADIOTHERAPY ; RADIATION
资助项目National Natural Science Foundation of China[22074043] ; National Natural Science Foundation of China[32311530041] ; National Natural Science Foundation of China[U22A20328] ; Science and Technology Commission of Shanghai Municipality[23ZR1475000] ; Science and Technology Commission of Shanghai Municipality[20430711800] ; Science and Technology Commission of Shanghai Municipality[23490712700] ; State Key Laboratory of Chemical Biology, Shandong Postdoctoral Science Foundation[SDCX-ZG-202400071] ; Shanghai Post-doctoral Excellence Program[2023696] ; China Postdoctoral Science Foundation[2023M743657] ; Postdoctoral Fellowship Program of CPSF[GZC20232844]
WOS研究方向Science & Technology - Other Topics
WOS记录号WOS:001355853200015
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/314524]  
专题新药研究国家重点实验室
通讯作者Xu, Zhiai
作者单位1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
2.Chinese Acad Sci, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Small Mol Drug Res Ctr, Shanghai 201203, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Biotherapeut Discovery Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Hou, Bo,Ye, Jiayi,Huang, Lujia,et al. Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy[J]. SCIENCE ADVANCES,2024,10(46):17.
APA Hou, Bo.,Ye, Jiayi.,Huang, Lujia.,Cheng, Wenhao.,Chen, Fangmin.,...&Xu, Zhiai.(2024).Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy.SCIENCE ADVANCES,10(46),17.
MLA Hou, Bo,et al."Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy".SCIENCE ADVANCES 10.46(2024):17.

入库方式： OAI收割

来源：上海药物研究所

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