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

Magnetic iron oxide nanoparticles (Fe 3 O 4 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 Fe 3 O 4 NPs is herein communicated by platinum (Pt) decoration, due to its inertness and low surface-ligand exchange rate. This not only prevents Fe 3 O 4 NP degradation in harsh biological media but also preserves their magnetism and enables rapid and stable modification of ligands, yielding high-fidelity Fe 3 O 4 @Pt probes. Benefiting from the high stability, the functionalized Fe 3 O 4 @Pt NPs demonstrated much higher sensitivity and reliability for biomarker detection in thiol-interfered fluids compared to structurally analogous Fe 3 O 4 @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 Fe 3 O 4 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.