Photothermal Enhanced and Tumor Microenvironment Responsive-Nanozyme for Amplified Cascade Enzyme Catalytic Therapy.

Nanocatalysts, a class of nanomaterials with intrinsic enzyme-like activities, have been widely investigated for cancer catalytic therapy in recent years. However, precisely construction of nanocatalysts with excellent enzyme catalytic activity and biosafety for tumor therapy still remain challenges. Here, we report a biodegradable nanocatalyst, PEGylated Cu x Mn y S z (PCMS), that can promote cascade catalytic reactions in tumor microenvironment (TME) while confining off-target side effects on normal tissues. PCMS not only catalyzes the cascade conversion of endogenous hydrogen peroxide (H 2 O 2 ) to oxygen (O 2 ) via catalase-like activity and then to superoxide radical (⚫O 2 - ) via oxidase-like activity in TME, but also effectively depletes intracellular glutathione via glutathione oxidase-like activity. The cascade catalytic reactions, by taking advantage of high H 2 O 2 level in tumor cells, result in an enhanced enzyme catalytic effect in generation of ⚫O 2 - . More importantly, PCMS exhibits prominent photothermal effect under NIR-II 1064 nm laser irradiation that can further enhanced chemodynamic therapy (CDT) efficacy in tumor. In addition, the biodegradation in TME and excellent photothermal effect of PCMS are beneficial to magnetic resonance imaging, photoacoustic imaging and infrared thermal imaging, respectively, resulting in tracing the fate of PCMS in vivo. This study provides a new clue for rational design of TME-responsive nanocatalysts with high biocompatibility for tumor catalytic therapy. This article is protected by copyright. All rights reserved.