Dual-Targeting and Multimodal Imaging-Guided Photothermal/ Chemodynamic Synergistic Therapy Boosted by Ascorbic Acid- Induced H2O2 in Situ Self-Supply

Tumor-specific targeting and tumor visualization are major obstacles for clinical diagnosis and treatment. Herein, a dual-targeted "all-in-one" nanoplatform (FAA@CM) for trimodal imaging-guided photothermal/chemodynamic synergistic therapy was successfully synthesized by encapsulating Fe3O4, Ag2S, and ascorbic acid with the 4T1 cell membrane. The dual-targeting capability derived from 4T1 cell membrane cloaking and magnetic targeting enables the highly precise tumor-specific delivery of FAA@CM. Fe2+ released from FAA@CM in a weakly acidic tumor microenvironment can trigger the Fenton reaction to achieve chemodynamic therapy (CDT). The photothermal performance of FAA@CM not only enables photothermal therapy but also promotes the CDT effect. In order to relieve H2O2 deficiency, a biosafe H2O2 prodrug, ascorbic acid, was introduced to greatly increase the H2O2 concentration in tumors, promoting the Fenton reaction to produce more center dot OH to enhance the oxidative damage to tumors. Interestingly, FAA@CM exhibits trimodal imaging capabilities, including second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging, photoacoustic imaging, and magnetic resonance imaging, which can guide the laser irradiation, achieving complete elimination of 4T1 tumors in BALB/c mice. This work provided a novel dual-targeted, multifunctional theranostic nanoplatform for highly effective tumor therapy.