Cascade Nanoreactor Based on Mo₂C MXene for NIR-II-Activated Multimodal Therapy of Cancer

The complexity and dynamic nature of the tumor microenvironment (TME) pose significant challenges to effective cancer therapy. Therefore, the development of nanocomposites capable of fully exploiting TME characteristics is crucial for achieving precise and efficient tumor treatment. Herein, the cascade nanoreactor PDA@Mo₂C-MnO₂-Au/Apt-M (PMMAA) was successfully constructed based on Mo₂C MXene and nanozymes. This nanoreactor leveraged the TME to achieve NIR-II-triggered combined photothermal therapy and chemodynamic therapy (PTT/CDT) with active targeting capability. PMMAA exhibited a photothermal conversion efficiency of 41.89% under NIR-II laser irradiation, enabling efficient thermal ablation of tumor tissues. In the acidic TME, the loaded MnO₂ NPs mediated Fenton-like reactions that selectively converted endogenous H₂O₂ into highly cytotoxic ^•OH, realizing intelligent TME-responsive CDT. Notably, the embedded Au NPs in the nanoreactor exhibited glucose oxidase-like activity, catalyzing the conversion of glucose into H₂O₂ and gluconic acid, thereby simultaneously elevating both H₂O₂ levels and local acidity to establish a self-amplifying catalytic cascade. This nanozymes-based cascade amplification effect significantly enhanced CDT efficacy by promoting ^•OH generation. Systematic evaluations demonstrated that the nanoreactor possessed dual enzyme-mimicking activities (POD-like and GOx-like), excellent biosafety, and remarkable tumor suppression effects. This study established a new paradigm for precision cancer therapy through the rational design of multifunctional nanozymes-enhanced CDT capable of dynamically modulating the TME.