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

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 ) 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 can catalyze endogenous H O into O and subsequently accelerating glucose oxidation by Au NPs to produce additional H O , which is reversely used as the substrate for MnO -catalyzed reaction, thereby constantly producing singlet oxygen ( O ) 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.