Electro‐Driven Surface‐Plus PtIr Nanocatalyst Degradation and Ion Channel Activation for Enhanced Tumor Dynamic Metal‐ion Therapy with Minimal Toxicity

Abstract Electrodynamic therapy (EDT), with its unique advantages, has demonstrated promising therapeutic effects in tumor treatment. However, its efficiency is often limited by the low concentration of chloride ions (Cl⁻) within tumor cells, and the non‐degradability of the noble metal nanomaterials necessarily used in this strategy gives rise to safety concerns. Here, we identify voltage‐gated chloride channels (CLC‐7) as a potential chloride‐regulation target in melanoma and report an enhanced electro‐driven dynamic therapy strategy utilizing surface‐enhanced PtIr@M nanocatalysts to address above challenges. Under an alternating electric field (AEF), the activation of CLC‐7 channel promotes a massive influx of Cl⁻ from the extracellular side and enhances the catalysis of water dissociation on PtIr@M nanocatalysts to generate toxic hydroxyl radicals (·OH). Moreover, PtIr@M with large surface area provides abundant exposed active sites that facilitate electro‐driven self‐dissociation and followed release of metal Pt ions, thereby inducing the DNA damage. More importantly, this electrically controlled degradation also effectively minimizes the toxicity associated with heavy metal accumulation. It is believed that this electro‐propelled ·OH and Pt ions generation for synergetic tumor therapy based on surface‐plus PtIr nanocatalyst represents a promising therapeutic strategy characterized by high‐efficiency and biodegradability.