Engineering Protein–Nanoparticle\nHybrids as\nTargeted Contrast Agents

Iron oxide nanoparticles (IONPs) have shown great promise\nin biomedical\napplications, particularly as MRI contrast agents due to their magnetic\nproperties and biocompatibility. Although several IONPs have been\napproved by regulatory agencies as MRI contrast agents, their primary\napplication as negative contrast agents limits their usage. Additionally,\nthere is an emerging need for the development of molecular contrast\nagents that can specifically target biomarkers, enabling more accurate\nand sensitive diagnostics. To address these challenges, we exploited\nthe engineerability of proteins to stabilize IONPs with tailored magnetic\nproperties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs)\nand leveraged the chemical diversity of proteins to functionalize\nProt-IONPs with targeting moieties. As a proof-of-concept, we used\nalendronate (Ald) to target atherosclerotic plaques in the aorta.\nSimple protein functionalization allowed targeting while maintaining\nthe stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald\nsuccessfully enabled positive contrast imaging of atherosclerotic\nplaques <i>in vivo</i> in an atherosclerotic mouse model\n(ApoE<sup>–/–</sup> mice on a high-fat diet). This study\ndemonstrates the potential of engineering protein–nanoparticle\nhybrids as versatile platforms for developing targeted <i>in\nvivo</i> MRI contrast agents.