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

Abstract

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.