A Dual‐Nanozyme‐Catalyzed Cascade Reactor for Enhanced Photodynamic Oncotherapy against Tumor Hypoxia

Abstract Tumor hypoxia is a typical characteristic of tumor microenvironment (TME), which seriously compromises the therapeutic effect of photodynamic therapy (PDT). The development of nanozymes with oxygen‐generation ability is a promising strategy to overcome the oxygen‐dependent of PDT but remained a great challenge. Herein, a dual‐nanozymes based cascade reactor HAMF is proposed to alleviate tumor hypoxia for enhanced PDT. The hollow mesoporous silica nanoparticles (HMSNs) are constructed as an excellent nanocarrier to load ultra‐small gold nanoparticles (Au NPs) and manganese dioxide (MnO 2 ) shell via in situ reduction method, and further coordination with an efficient photosensitizer 4‐DCF‐MPYM (4‐FM), a thermally activated delayed fluorescence (TADF) fluorescein derivative. With the response to TME, MnO 2 can catalyze endogenous H 2 O 2 into O 2 and subsequently accelerating glucose oxidation by Au NPs to produce additional H 2 O 2 , which is reversely used as the substrate for MnO 2 ‐catalyzed reaction, thereby constantly producing singlet oxygen ( 1 O 2 ) for enhanced PDT upon light irradiation. This work proposed a cascade reactor based on dual‐nanozyme to relieve tumor hypoxia for effective tumor suppression, which may enrich the application of multi‐nanozymes in biomedicine.