Triple cascade nanocatalyst with laser-activatable O2 supply and photothermal enhancement for effective catalytic therapy against hypoxic tumor

Nanozymes have been combined with glucose oxidase (GOx) for dual-enzyme cascade catalytic therapy. However, their catalysis efficiency is restricted because of the hypoxia tumor microenvironment (TME). Although many methods are developed for O2 supply, the O2 leakage and consumption of H2O2 compromised their practical application. Herein, a biocompatible carbon nitride (C3N4)/nanozyme/GOx triple cascade nanocatalyst was designed with laser-activatable O2 self-supply via water splitting to relieve tumor hypoxia and thus improve the catalysis efficiency. To this end, polydopamine (PDA) nanosphere was prepared and attached with C3N4 nanosheet to improve water splitting efficiency and realize photothermal-enhanced catalysis, simultaneously. The PDA@C3N4 composite was then coated with MIL-100 (Fe), where GOx was loaded, to form C3N4/MIL-100/GOx triple cascade nanocatalyst. The triple cascade catalysis was realized with laser-activatable O2 supply from PDA@C3N4, H2O2 generation with GOx, and •OH production from peroxidase-like MIL-100 (Fe) for tumor therapy. Upon 808 nm irradiation, PDA, as a photothermal agent, realized photothermal therapy and enhanced the catalytic therapy. Thus, the synergy of laser-activatable O2 supply and photothermal enhancement in our triple cascade nanocatalyst improved the performance of catalytic therapy without drug resistance and toxicity to normal tissues.