Perylene‐Mediated Cytoskeletal Dysfunction Remodels Cancer‐Associated Fibroblasts to Augment Antitumor Immunotherapy

Abstract Targeted reprogramming cancer‐associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs towards deactivated state still remains immense challenges. To tackle this challenge, we herein prepared one perylene PDIC‐OC, 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, down‐regulation of alpha‐smooth muscle actin (α‐SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realized outstanding anti‐tumor 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. This article is protected by copyright. All rights reserved