Cu‐Doped Polypyrrole with Multi‐Catalytic Activities for Sono‐Enhanced Nanocatalytic Tumor Therapy

Abstract Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst‐initiated therapeutics. Here, a Cu‐doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi‐catalytic activities, including catalyzing H 2 O 2 to generate O 2 and · OH, and consuming reduced glutathione by a Cu(II)‐Cu(I) transition approach. By decorating with sonosensitizers and DSPE‐PEG, the obtained CuPPy‐TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor‐specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress‐based antitumor therapy.