Deep Downregulation of PD‐L1 by Caged Peptide‐Conjugated AIEgen/miR‐140 Nanoparticles for Enhanced Immunotherapy. Issue 18 (9th March 2022)

• Record Type: Journal Article
• Authors: Dai, Jun; Hu, Jing‐Jing; Dong, Xiaoqi; Chen, Biao; Dong, Xiyuan; Liu, Rui; Xia, Fan; Lou, Xiaoding
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 18(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-09
• Subjects: Aggregation-Induced Emission -- Immunotherapy -- MicroRNA -- Peptide -- Programmed Death Ligand 1; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202117798
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : In tumor cells, a caged peptide‐AIEgen probe self‐assembled with miR‐140 could release the GO203 peptide binding to MUC1 and miR‐140 degrading the PD‐L1 mRNA, thus, achieving the deep downregulation of the PD‐L1 expression. Subsequently, activated immune cells by PDT‐induced release of TAAs would achieve more effective immunotherapy.