Affiliation:
1. Laboratory for NanoMedical Photonics School of Basic Medical Science Henan University Zhengzhou Henan 475001 P. R. China
2. Life and Health Intelligent Research Institute Tianjin Key Laboratory of Life and Health Detection Tianjin University of Technology Tianjin 300387 P. R. China
Abstract
AbstractTargeted reprogramming of cancer‐associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'‐bis(2‐((dimethylammonium)ethylene)‐2‐(methoxylethyl))‐1, 6, 7, 12‐tetrachloroperylene‐3, 4, 9, 10‐tetracarboxylic diimide (PDIC‐OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor β (TGF‐β) production. As a result, PDIC‐OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2‐typed macrophages into M1‐typed ones, downregulation of alpha‐smooth muscle actin (α‐SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor‐xenografted and lung‐metastatic mouse model even at low concentration of 1 mg kg−1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF‐β to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene‐triggered chemo‐immunotherapy against hypoxic tumors.
Funder
National Natural Science Foundation of China
Henan University
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials