Multiple valence states of Fe boosting SERS activity of Fe₃O₄ nanoparticles and enabling effective SERS-MRI bimodal cancer imaging

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment. Herein, an optimized strategy for designing a Fe₃O₄-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI) is introduced. Excellent SERS activity of ultrasmall Fe₃O₄ nanoparticles (NPs) was discovered, and a 5 × 10⁻⁹ M limit of detection for crystal violet molecules was successfully obtained. The high-efficiency interfacial photon-induced charge transfer in Fe₃O₄ NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe, which was observed using ultraviolet–visible diffuse reflectance spectroscopy. Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe₃O₄ NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination. The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Fe₃O₄-based bioprobe with high sensitivity and good specificity. Notably, Fe₃O₄-based bioprobes simultaneously exhibited T₁-weighted MRI contrast enhancement with an active targeting capability for tumors in vivo. To the best of our knowledge, this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro, which has been previously realized only using semiconductor–metal complex materials. The non-metallic materials with SERS–MRI dual-modal imaging established in this report are a promising cancer diagnostic platform, which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.