Multifunctional cascade nanocatalysts for NIR-II-synergized photonic hyperthermia-strengthened nanocatalytic therapy of epithelial and embryonal tumors

Chemodynamic therapy, which produces cytotoxic hydroxyl radicals through intratumoral Fenton reactions, has been extensively explored in nanomedicine for cancer treatment. However, the limited endogenous hydrogen peroxide (H2O2) levels, which serve as the reactant, weakens the anticancer effect of the Fenton reaction. In this work, a cascade catalytically reactive nanosystem has been constructed for the treatment of epithelial and embryonal tumors with high synergetic efficacy through the integration of natural glucose oxidase (GOD) and polyethylene glycol (PEG) onto the surface of Fe3S4 nanoplates (abbreviated as Fe3S4-PEG-GOD NPs). The GOD component consumes glucose in tumor and produces a large amount of H2O2, which provides rich substrates for the Fenton reaction catalyzed by the Fe catalytic center of the nanoplates. The intriguing photothermal conversion efficiency (45%) of the constructed composite nanocatalysts in the second near infrared (NIR-II) biowindow allows for photothermal treatment to substantially strengthen and synergize the anticancer effects of nanocatalysts both in vitro and in vivo. This synergy occurs through generation of a hyperthermic effect necessary for promoting the sequential catalytic reaction. The synergistic anticancer effect has been verified in both epithelial and embryonal tumor mouse models, and provides justification for the biomedical use of multifunctional nanocatalysts for versatile tumor nanotherapeutics.