ABSTRACT Ischemia‐reperfusion injury (IRI) paradoxically aggravates tissue damage after blood flow restoration. While current antioxidant and anti‐inflammatory strategies offer partial benefits, their limited efficacy underscores the need for more targeted, mechanism‐driven interventions. Ferroptosis, an iron‐dependent form of regulated cell death driven by lipid peroxidation and glutathione peroxidase 4 (GPX4) inactivation, has recently emerged as a unifying pathological axis in IRI across multiple organs including the brain, heart, liver, and kidneys. Its non‐apoptotic nature and centrality in oxidative damage position ferroptosis as a compelling target for therapeutic innovation. Concurrently, advances in nanomedicine offer transformative tools for modulating ferroptosis with spatial and temporal precision. Nanoplatforms equipped with iron chelators, antioxidant cargos, ferroptosis inhibitors, or stimuli‐responsive architectures can selectively accumulate in injured tissues, respond to pathological microenvironments, and deliver therapeutic payloads with enhanced efficacy. This review systematically explores the molecular basis of ferroptosis, its role in IRI pathophysiology, and the latest advances in nanomedicine‐based interventions. It further discusses translational challenges, such as long‐term biosafety and limited tissue targeting, and outlines future directions toward intelligent degradable nanomaterials and humanized models. By bridging ferroptosis biology with cutting‐edge nanotechnology, this emerging field offers a paradigm shift toward precision medicine in oxidative injury and beyond.
Sun et al. (Wed,) studied this question.