High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO₂ shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO₂ shell would deplete glutathione (GSH) and produce Mn²⁺, while a large amount of H₂O₂ generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn²⁺, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO₂ would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.