Highly Efficient GSH-Responsive “Off–On” NIR-II Fluorescent Fenton Nanocatalyst for Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Cancer Therapy

Accurate diagnosis and effective treatment of malignant tumors under the interference of complex and diverse tumor microenvironments (TMEs) have become the focus of research. Herein, an innovative TME-activated biomimetic nanocatalyst with quad-modal imaging capabilities of second near-infrared (NIR-II) "turn-on" fluorescence imaging, magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal imaging (PTI) was designed and developed for self-enhanced photothermal/chemodynamic synergistic therapy. The catalyst was fabricated by loading glucose oxidase (GOD) and Ag₂S quantum dots (QDs) on MnO₂ nanosheets and coating them with a 4T1 cell membrane (AMG@CM), which enables them to successfully escape immune clearance and have appealing tumor-targeting ability and biocompatibility. The NIR-II fluorescence at 1130 nm of Ag₂S QDs quenched by MnO₂ could be recovered in vivo through the glutathione (GSH)-induced degradation of MnO₂, enabling excellent TME-responsive tumor visualization. Simultaneously, the released Mn²⁺ can catalyze H₂O₂ to produce abundant hydroxyl radicals (•OH), achieving photothermal synergistically enhanced chemodynamic therapy (CDT) under NIR-II radiation. Moreover, the CDT could be self-enhanced by GOD due to the extra produced H₂O₂. This work demonstrates a novel and highly efficient multimodal imaging-guided integrated treatment strategy for dual-enhanced CDT tumor precise diagnosis and treatment.