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 O 2 supply, the O 2 leakage and consumption of H 2 O 2 compromised their practical application. Herein, a biocompatible carbon nitride (C 3 N 4 )/nanozyme/GOx triple cascade nanocatalyst was designed with laser-activatable O 2 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 C 3 N 4 nanosheet to improve water splitting efficiency and realize photothermal-enhanced catalysis, simultaneously. The [email protected] 3 N 4 composite was then coated with MIL-100 (Fe), where GOx was loaded, to form C 3 N 4 /MIL-100/GOx triple cascade nanocatalyst. The triple cascade catalysis was realized with laser-activatable O 2 supply from [email protected] 3 N 4 , H 2 O 2 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 O 2 supply and photothermal enhancement in our triple cascade nanocatalyst improved the performance of catalytic therapy without drug resistance and toxicity to normal tissues.