Superparamagnetic iron oxide nanoparticles - From synthesis to nanomedicine

Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as powerful tools in nanomedicine owing to their heavy-metal-free composition, distinct magnetic properties, biocompatibility, and customizable surface chemistry. While traditionally employed as T₂-weighted MRI contrast agents, recent innovations have enabled the development of ultra-small SPIONs-such as exceedingly small SPIONs (ES-SPIONs) and single-nanometer iron oxide nanoparticles (SNIOs)-that offer T₁-weighted MRI capabilities, which are favored by radiologists for their superior anatomical clarity. This review highlights the synthesis of monodisperse SPIONs via thermal decomposition and controlled oxidation, as well as their functionalization with zwitterionic dopamine sulfonate (ZDS) ligands, which confer colloidal stability, minimal protein adsorption, and efficient renal clearance. Notably, SNIOs conjugated with collagen-binding peptides (CBPs) enabled rapid, non-invasive detection of liver fibrosis, comparable to mainstream gadolinium-based probes in sensitivity. We further discuss the integration of SPIONs with fluorescent quantum dots to achieve magneto-fluorescent constructs for dual-modal imaging, facilitating simultaneous MR and optical tracking. These advancements collectively position ZDS-coated SPIONs as potential MRI agents with theranostic potential, bridging the gap between fundamental nanoscience and clinical application. This review also addresses ongoing challenges in clinical translation, while outlining a forward-looking vision for SPIONs in personalized, non-invasive diagnostics, biosensing, and targeted therapeutics.