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Deep Downregulation of PD-L1 by Caged Peptide-Conjugated AIEgen/miR-140 Nanoparticles for Enhanced Immunotherapy

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan 430034, Peoples R China [2]China Univ Geosci, Fac Mat Sci & Chem, State Key Lab Biogeol & Environm Geol, Wuhan 430074, Peoples R China
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关键词: Aggregation-Induced Emission Immunotherapy MicroRNA Peptide Programmed Death Ligand 1

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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.

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出版当年[2021]版:
大类 | 1 区 化学
小类 | 1 区 化学综合
最新[2025]版:
大类 | 1 区 化学
小类 | 1 区 化学:综合
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出版当年[2020]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY
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Q1 CHEMISTRY, MULTIDISCIPLINARY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan 430034, Peoples R China
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