Noninvasive SERS Immunosensing of Tyrosinase for Melanoma Monitoring via Microneedle Sampling Integrated with Satellite-Structured Bifunctional Nanozymes.

The noninvasive and in situ monitoring of melanoma biomarkers remains a significant challenge in clinical diagnostics. This study reports a novel sensing platform that integrates a wearable microneedle (MN) patch with satellite-structured CoFe2O4-Au@Pt nanoparticles (NPs) featuring both highly efficient mimic enzyme and surface-enhanced Raman scattering (SERS) activity for detection of tyrosinase, aiming at melanoma monitoring. First, the MN patch facilitates the sampling of cutaneous interstitial fluid and the immunocapture of tyrosinase. Then, the captured tyrosinase is quantified using a SERS immunoassay, where the CoFe2O4-Au@Pt NPs serve as bifunctional materials of signal transducers and powerful SERS substrates. Their intrinsic oxidase-mimicking activity catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), while their superior SERS activity enables the highly sensitive readout of the oxidized TMB (oxTMB) product. The developed detection system demonstrates the capability to quantify TYR levels in skin models over a linear range of 0.01 ng/mL to 10 μg/mL, with a limit of detection (LOD) as low as 6.61 pg/mL. Notably, the system exhibits robust selectivity and strong anti-interference capacity against complex biological matrices. Using a preclinical B16F10 murine melanoma model, the platform successfully achieves the quantification of tyrosinase levels, demonstrating its capability to provide high-fidelity information for melanoma prognosis and longitudinal disease monitoring. Thus, the integration of MN-based sampling, nanozyme-mediated amplification, and in situ SERS detection paves the way for novel diagnostic approaches in melanoma management.