Clinical translation and landscape of superparamagnetic iron oxide nanoparticles

Since their initial clinical approval as liver imaging agents nearly three decades ago, superparamagnetic iron oxide nanoparticles (SPIONs) have evolved beyond diagnostic imaging to include also therapeutic and theranostic applications. Their clinical utility in both diagnosis and therapy depends on a combination of intrinsic physicochemical properties and in vivo behaviors, such as biodistribution and pharmacokinetics. These attributes enable specific applications, depending on the mechanisms of action and route of administration. For example, nanoparticle degradation can support anemia treatments. Tissue-specific retention in fenestrated organs and pathological tissues after systemic administration allows for imaging of the liver and inflammation sites, and image-guided therapy. Local delivery enables applications such as sentinel lymph node mapping and localized tumor thermal ablation. At the same time, these properties also constrain SPIONs from broader use as universal nanodiagnostic and theranostic agents. This review provides an overview of the current clinical landscape of superparamagnetic iron oxide nanoparticles, identifies shared features that have facilitated their successful translation, and discusses the critical challenges that must be addressed to enable wider clinical adoption.