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 <i>in vivo</i>. 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).