Ternary Alloy PtWMn as a Mn Nanoreservoir for High‐Field MRI Monitoring and Highly Selective Ferroptosis Therapy

Ferroptosis exhibits potential to damage drug‐resistant cancer cells. However, it is still restricted with the “off‐target” toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment‐triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high‐field magnetic resonance imaging (MRI), which enables the real‐time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1‐/T2‐MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI‐guided high‐specificity ferroptosis therapy. A novel ternary alloy PtWMn nanoplatform is developed as a Mn reservoir that exhibits efficient storage, specific delivery and accurate release of Mn ions for high‐specificity ferroptosis‐based cancer therapy. Such a smart nanoplatform can exert a responsive imaging signal in dual‐mode (T1‐ or T2‐weighted) high‐field MRI, which enables the real‐time monitoring of Mn release within the tumor microenvironment and of ferroptosis initiation.