Challenges and Future Prospects of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in Nanomedicine: A Focus on Toxicity, Imaging, and Theranostics

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have emerged as a pivotal tool in nanomedicine, offering potential in drug delivery, imaging, and targeted therapies. However, their application is challenged by issues such as cytotoxicity, uneven biodistribution, and biocompatibility. SPIONs are predominantly cleared through renal or hepatobiliary pathways, with size and charge playing critical roles in determining their fate. While smaller SPIONs optimize renal clearance, their propensity to agglomerate and activate macrophages may induce inflammatory responses. Radiolabeled SPIONs face additional challenges in molecular imaging and nuclear medicine. Emerging strategies, such as chelator-free radiolabeling and multi-component nanoparticles, aim to address these limitations by improving targeting specificity and enhancing biocompatibility. Looking forward, SPIONs hold immense potential in theranostics, particularly in integrating imaging with targeted drug delivery and therapies. Advances in synthesis and surface functionalization may enhance their safety and effectiveness. Future research should focus on optimizing SPIONs, integrating them with therapeutic agents, and improving targeting and clearance mechanisms. Collaboration among experts and the use of <i>Artificial Intelligence (AI)</i> modeling could accelerate their development for personalized treatment applications. This review uniquely highlights recent advances in radio-labeled SPIONs for molecular imaging and targeted therapy, addressing challenges like biocompatibility, stability, and translational applicability.