Plasmonic Photoenzymatic Therapy with SERS Monitoring for Oral Cancer

Traditional photodynamic therapy (PDT), chemodynamic therapy (CDT), and photothermal therapy (PTT) for oral squamous cell carcinoma (OSCC) face inherent limitations, including oxygen dependence, insufficient endogenous H₂O₂, and nonspecific thermal diffusion. To address these challenges, we developed a near infrared (NIR) responsive theranostic platform based on Au@RCDs@GOx. This system leverages a single NIR wavelength to trigger plasmon enhanced cascade therapy integrating PTT ablation, glucose oxidase (GOx) generated H₂O₂, photo amplified CDT, and starvation therapy. Importantly, photoexcited electrons are injected into the flavin adenine dinucleotide (FAD) cofactor of GOx via the red emitting carbon dots (RCD) shell, enabling sustained reactive oxygen species (ROS) generation even under glucose deprived conditions through direct 1-electron reduction of O₂ to superoxide anions (·O₂^-). Meanwhile, Au@RCDs@GOx exhibit excellent surface-enhanced Raman scattering (SERS) activity, providing real-time feedback on oxidative stress within the tumor microenvironment. In an OSCC xenograft model, intratumoral administration of this platform at an ultralow dose (0.12 mg kg^-1) achieved 95.7% tumor suppression with excellent biosafety. This work establishes photoenzymatic catalysis as an adaptive and synergistic paradigm for cancer therapy with integrated SERS monitoring.