A Unique Multifunctional Nanoenzyme Tailored for Triggering Tumor Microenvironment Activated NIR‐II Photoacoustic Imaging and Chemodynamic/Photothermal Combined Therapy

The accurate diagnosis and targeted therapy of malignant tumors face significant challenges. To address these, an oxidized molybdenum polyoxometalate-copper nanocomposite (Ox-POM@Cu) is designed and synthesized here. The doping with Cu determines the formation of oxygen vacancies, which can increase the carrier concentration in Ox-POM@Cu, accelerate electron transfer, and enhance the redox activity, thus playing an efficient catalytic role. The nanocomposite presents unique enzymatic functions characterized by a multielement catalytic activity in the tumor microenvironment (TME). In addition, it can be employed as an NIR-II photoacoustic imaging (PAI) probe and cancer therapy agent. First, it participates in a redox reaction with glutathione (GSH) in tumor tissues, activates the PAI and photothermal therapy functions via NIR-II irradiation, and depletes the GSH supply in cancerous cells. Subsequently, it catalyzes a Fenton-like reaction with H2 O2 in tumor tissues to form hydroxyl radicals, thereby performing a chemodynamic therapy function. The findings show that the developed nanoenzyme is very efficient in the diagnosis and treatment of malignant tumors. This work not only provides a new strategy for the design of TME-induced NIR-II PAI but also presents new insights into enhanced cancer therapy.