EDTA‐Functionalized Nanoscale Metal–Organic Framework for Onco‐Cardiology via Radiochemotherapy Synergy and Spatiotemporally Matched Iron Chelation

ABSTRACT Doxorubicin (DOX)‐induced cardiotoxicity (DIC) has become a major obstacle for clinical application. While ferroptosis represents a critical therapeutic target for DIC, current intervention strategies are limited by spatiotemporal mismatches between DOX accumulation and iron chelation. Here, we engineered an EDTA‐functionalized Hf‐based metal–organic framework for DOX delivery. This nanoplatform ( DME ) simultaneously mediates tumor radiochemotherapy synergy and inhibits ferroptosis via real‐time iron chelation in cardiac tissue. The EDTA modification not only enhances drug penetration to kill deep‐seated tumors, but also endows DME superior iron‐scavenging ability, which effectively suppresses mitochondrial‐dependent ferroptosis in cardiomyocytes. Using primary cultured neonatal mice cardiomyocytes and a chronic DIC murine model, we demonstrated DME ’s significant cardioprotection and elucidated its mechanistic basis. Thus, our work establishes a bifunctional nanoplatform that unifies oncotherapy and cardioprotection, offering a spatiotemporally matched iron‐chelation strategy for safe and effective clinical use of DOX.