Implanted, Wireless, Self‐Powered Photodynamic Therapeutic Tablet Synergizes with Ferroptosis Inducer for Effective Cancer Treatment

Abstract The effective and targeted treatment of resistant cancer cells presents a significant challenge. Targeting cell ferroptosis has shown remarkable efficacy against apoptosis‐resistant tumors due to their elevated iron metabolism and oxidative stress levels. However, various obstacles have limited its effectiveness. To overcome these challenges and enhance ferroptosis in cancer cells, we have developed a self‐powered photodynamic therapeutic tablet that integrates a ferroptosis inducer (FIN), imidazole ketone erastin (IKE). FINs augment the sensitivity of photodynamic therapy (PDT) by increasing oxidative stress and lipid peroxidation. Furthermore, they utilize the Fenton reaction to supplement oxygen, generating a greater amount of reactive oxygen species (ROS) during PDT. Additionally, PDT facilitates the release of iron ions from the labile iron pool (LIP), accelerating lipid peroxidation and inducing ferroptosis. In vitro and in vivo experiments have demonstrated a more than 85% tumor inhibition rate. This synergistic treatment approach not only addresses the limitations of inadequate penetration and tumor hypoxia associated with PDT but also reduces the required medication dosage. Its high efficiency and specificity towards targeted cells minimize adverse effects, presenting a novel approach to combat clinical resistance in cancer treatment.