d-Penicillamine-loaded MIL-100(Fe) for precise targeted copper chelation in Wilson's disease

Wilson's disease (WD) is a genetic disorder of copper metabolism that causes severe impairment of liver and brain functions, urgently requiring safe and effective chelation strategies. Herein, this work highlights the successful construction of a ROS-responsive nanoplatform (MIL-100(Fe)-DPA), which is facilely fabricated by encapsulating d-penicillamine (DPA) into the porous framework of MIL-100(Fe). The nanocomposite exhibits a stable crystalline structure, uniform nano size, excellent hemocompatibility, and high drug loading efficiency, while maintaining remarkable blood circulation stability. Importantly, its unique ROS-responsiveness enables targeted drug release under pathological copper-overloaded conditions, thereby achieving enhanced copper chelation and reduced systemic toxicity. In vivo studies demonstrate that MIL-100(Fe)-DPA markedly decreases hepatic copper accumulation, improves ALT and AST levels, restores hepatic architecture, and alleviates copper-induced tissue injury compared to free DPA. These attractive features indicate that MIL-100(Fe)-DPA represents a promising nanoplatform for precise copper chelation therapy, providing an effective therapeutic strategy for WD and related hepatic disorders.