NIR-II Type I AIE Photosensitiser-Functionalized MOF-Cu Nanoplatform Promotes Ferroptosis and Cuproptosis for Antitumor Therapy.

Cancer therapeutic strategies centered on synergistic ferroptosis and cuproptosis have attracted considerable interest. However, current approaches predominantly relying on Fe and Cu sources face limitations including single mode of reactive oxygen species (ROS) production, poor organelle targeting, and lack of imaging capabilities. Herein, we developed a multifunctional nanoplatform, NMC NPs, by integrating a type I aggregation-induced emission photosensitizer (NTI) with a Cu-based nanozyme (MOF-Cu). This design enables efficient ROS generation, precise mitochondria targeting, and real-time fluorescence imaging, allowing more effective activation of ferroptosis and cuproptosis. Upon cellular uptake, MOF-Cu framework dissociates and releases NTI, which selectively accumulates in mitochondria. Under 635 nm laser irradiation, NTI generates type I ROS, triggering lipid peroxidation and activating ferroptosis. Simultaneously, MOF-Cu nanozyme exerts dual peroxidase-like and glutathione peroxidase-like activities, catalyzing H