Surface Passivation of Fe3O4 Nanoparticles: Avoiding Degradation, Preserving Magnetism, and Facilitating Ligand Modification for Better Biomedical Analysis

Magnetic iron oxide nanoparticles (Fe3O4 NPs) hold great potential for biomedical applications, yet their structural degradation and function loss under physiological conditions limit practical utility. To improve their performance, a surface passivation strategy for Fe3O4 NPs is herein communicated by platinum (Pt) decoration, due to its inertness and low surface-ligand exchange rate. This not only prevents Fe3O4 NP degradation in harsh biological media but also preserves their magnetism and enables rapid and stable modification of ligands, yielding high-fidelity Fe3O4@Pt probes. Benefiting from the high stability, the functionalized Fe3O4@Pt NPs demonstrated much higher sensitivity and reliability for biomarker detection in thiol-interfered fluids compared to structurally analogous Fe3O4@Au NPs. Clinical detection of urine miR-200c from bladder cancer patients further confirmed its diagnostic superiority, achieving 93% sensitivity and 93% specificity with an area under the curve of 0.982. This design opens a new path to advance Fe3O4 NPs performance and is adaptable to other magnetic nanomaterials by simply coating a Pt shell, offering transformative potential for better biomedical applications, such as high-efficiency bioseparation, high-fidelity diagnosis, and targeted therapeutics.