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

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‐1...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-04, Vol.61 (18), p.e202117798-n/a
Main Authors: Dai, Jun, Hu, Jing‐Jing, Dong, Xiaoqi, Chen, Biao, Dong, Xiyuan, Liu, Rui, Xia, Fan, Lou, Xiaoding
Format: Article
Language:English
Subjects:
Aggregation-Induced Emission
Antigen (tumor-associated)
Antigens
Apoptosis
B7-H1 Antigen - genetics
Cathepsin B
Cell death
Cell Line, Tumor
Down-Regulation
Immune system
Immunotherapy
MicroRNA
MicroRNAs - genetics
mRNA
Mucin
Nanoparticles
PD-L1 protein
Peptide
Peptides
Peptides - metabolism
Photodynamic therapy
Programmed Death Ligand 1
Tumor cells
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202117798