Redox‐Activatable Magnetic Nanoarchitectonics for Self‐Enhanced Tumor Imaging and Synergistic Photothermal‐Chemodynamic Therapy

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent malignancy of the head and neck region associated with high recurrence rates and poor prognosis under current diagnostic and treatment methods. The development of nanomaterials that can improve diagnostic accuracy and therapeutic efficacy is of great importance for OSCC. In this study, a redox‐activatable nanoarchitectonics is designed via the construction of dual‐valence cobalt oxide (DV‐CO) nanospheres, which can serve as a contrast agent for magnetic resonance (MR) imaging, and exhibit enhanced transverse and longitudinal relaxivities through the release and redox of Co 3+ /Co 2+ in an acidic condition with glutathione (GSH), resulting in self‐enhanced T 1 /T 2 ‐weighted MR contrast. Moreover, DV‐CO demonstrates properties of intracellular GSH‐depletion and hydroxyl radicals (•OH) generation through a Fenton‐like reaction, enabling strengthened chemodynamic (CD) effect. Additionally, DV‐CO displays efficient near‐infrared laser‐induced photothermal (PT) effect, thereby exhibiting synergistic PT‐CD therapy for suppressing OSCC tumor cells. It further investigates the tumor‐specific self‐enhanced MR imaging of DV‐CO both in subcutaneous and orthotopic OSCC mouse models, and demonstrate the therapeutic effects of DV‐CO in orthotopic OSCC mouse models. Overall, the in vitro and in vivo findings highlight the excellent theranositc potentials of DV‐CO for OSCC and offer new prospects for future advancement of nanomaterials.