Iron Knights with Nanosword Induced Ferroptosis in the Battle Against Oral Carcinoma

Oral squamous cell carcinoma (OSCC) is a tumor characterized by cellular redox imbalance, rendering it particularly sensitive to ferroptosis treatment. However, traditional ferroptosis inducers have a few drawbacks. In this study, ultrasmall AuMn nanoclusters (AMNCs) with a bovine serum albumin (BSA) ligand were synthesized and encapsulated in natural killer (NK) cell-derived exosomes to form an Exo-AMNCs composite for targeted ferroptosis therapy of OSCC. Unlike previously reported alloyed metal nanoclusters, not only do AMNCs react with intracellular H2O2 to produce reactive oxygen species (ROS) and induce ferroptosis but also the BSA ligand improves biocompatibility and water solubility. These properties render AMNCs ideal for fluorescence imaging in vivo. When combined with NK cell exosomes, the Exo-AMNCs composite exhibited strong targeted imaging and therapeutic effects on OSCC. Further investigation into the mechanistic details demonstrated that Exo-AMNCs downregulate the overexpression of fat mass and obesity-associated (FTO) in OSCC and regulate the key ferroptosis-related protein glutathione peroxidase 4 (GPX4).