Oxygen-Vacancy Engineered MoO_3-x@PEG Nanosheets for NIR-II-Triggered Cascade-Amplified Synergistic Cancer Therapy

Phototherapy holds great promise for cancer treatment due to its noninvasive nature and high spatiotemporal precision. However, its efficacy is often limited by the complex tumor microenvironment (TME). Herein, we report NIR-II-responsive PEGylated MoO_3-x nanosheets (MoO_3-x@PEG) synthesized via a one-step solvothermal method for synergistic photothermal (PTT), photodynamic (PDT), and chemodynamic therapy (CDT). The oxygen-vacancy rich structure endows MoO_3-x@PEG with enhanced NIR-II absorption, a narrowed bandgap (1.35 eV), and a high mass extinction coefficient (4.11 L·g^-1·cm^-1), leading to a superior photothermal conversion efficiency of 44.88%. The defect-engineered electronic structure also promotes electron-hole separation and facilitates reactive oxygen species (ROS) generation. Moreover, the Mo⁵⁺/Mo⁶⁺ redox pairs enable Fenton-like hydroxyl radical (^•OH) production in the acidic TME. Notably, NIR-II-induced photothermal heating further accelerates both singlet oxygen (¹O₂) and ^•OH generation, establishing a cascade amplification effect among PTT, PDT, and CDT. This work presents a multifunctional nanoplatform for enhanced tumor therapy via a single NIR-II trigger.