Vacancy engineering enhanced photothermal-catalytic properties of Co9S8−x nanozymes for mild NIR-II hyperthermia-amplified nanocatalytic cancer therapy†

While nanozymes are commonly employed in nanocatalytic therapy (NCT), the efficacy of NCT is hampered by the limited catalytic activity of nanozymes and the intricate tumor microenvironment (TME). In this work, we design a high-efficiency nanozyme with NIR-II photothermal property for the mild hyperthermia-augmented NCT. In order to endow a single-component nanomaterial the ability to simultaneously catalyze and exhibit NIR-II photothermal properties, a straightforward template method is utilized to fabricate sulfur vacancies (V_S)-doped Co₉S_8−x nanocages. Introducing V_S not only lowers the bandgap structure of Co₉S₈, enhancing its NIR-II photothermal properties, but also facilitates the control of the Co²⁺ and Co³⁺ ratio in Co₉S₈, leading to a boost in its catalytic activity. Furthermore, the catalytic efficiency of Co₉S_8−x nanocages was boosted by the mild hyperthermia. Moreover, the Co₉S_8−x nanocages exhibited high-efficiency GSH-px-mimic catalytic activity, facilitating the cascade amplification of ROS production. Through the integrated multifunctionality of Co₉S_8−x nanocages, we successfully enhanced the effectiveness of antitumor treatment with a single drug injection and a single 1064 nm laser irradiation for mild hyperthermia-augmented NCT. This work provides a distinct paradigm of endowing nanomaterials with catalytic activity and photothermal property for mild NIR-II PTT-amplified NCT through a vacancy engineering strategy.