Downregulating programmed cell death ligand 1(PD-L1) protein levels in tumor cells is an effective way to achieve immune system activation for oncology treatment, but current strategies are inadequate. Here, we design a caged peptide-AIEgen probe (GCP) to self-assemble with miR-140 forming GCP/miR-140 nanoparticles. After entering tumor cells, GCP/miR-140 disassembles in the presence of Cathepsin B (CB) and releases caged GO203 peptide, miR-140 and PyTPA. Peptide decages in the highly reductive intracellular environment and binds to mucin 1 (MUC1), thereby downregulating the expression of PD-L1. Meanwhile, miR-140 reduces PD-L1 expression by targeting downregulation of PD-L1 mRNA. Under the action of PyTPA-mediated photodynamic therapy (PDT), tumor-associated antigens are released, triggering immune cell attack on tumor cells. This multiple mechanism-based strategy of deeply downregulating PD-L1 in tumor cells activates the immune system and thus achieves effective immunotherapy.
基金:
National Key R&D Program of China [2020YFA0211200, 2021YFA1200403, 2018YFE0206900]; National Natural Science Foundation of China [22090050, 22104040, 21974128, 21874121, 52003257]; Joint NSFC-ISF Research Grant Program [22161142020]; Natural Science Foundation of Hubei Province [2020CFA037]; Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan 430034, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Dai Jun,Jing-Jing Hu,Dong Xiaoqi,et al.Deep Downregulation of PD-L1 by Caged Peptide-Conjugated AIEgen/miR-140 Nanoparticles for Enhanced Immunotherapy[J].ANGEWANDTE CHEMIE-INTERNATIONAL EDITION.2022,61(18):doi:10.1002/anie.202117798.
APA:
Dai, Jun,Jing-Jing Hu,Dong, Xiaoqi,Chen, Biao,Dong, Xiyuan...&Lou, Xiaoding.(2022).Deep Downregulation of PD-L1 by Caged Peptide-Conjugated AIEgen/miR-140 Nanoparticles for Enhanced Immunotherapy.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,61,(18)
MLA:
Dai, Jun,et al."Deep Downregulation of PD-L1 by Caged Peptide-Conjugated AIEgen/miR-140 Nanoparticles for Enhanced Immunotherapy".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 61..18(2022)