Highly Specific and Fast-Responsive Semicarbazide-Sensitive Amine Oxidase Nanoprobe for the Serological Diagnosis of Parkinson’s Patients

Semicarbazide-sensitive amine oxidase (SSAO), a multifunctional enzyme associated with various diseases, including neurodegenerative disorders, has emerged as a potential biomarker for Parkinson’s disease (PD). However, current SSAO detection methods, such as immunoassays and mass spectrometry, are limited by their complexity, nonselectivity, high cost, and the use of hazardous radioactive materials. In this study, we developed a highly specific, sensitive, and cost-effective method for SSAO activity detection based on optical gold nanoparticles (AuNPs). By functionalizing AuNPs with rationally designed β-mercaptoethylamine (MEA), the nanoprobe AuNPs@MEA enabled SSAO-specific oxidation, leading to the formation of aldehyde groups and subsequently mediating AuNPs’ aggregation via both Schiff base coupling and electrostatic interactions. This distinct change in the absorption spectrum allowed for quantitative detection of SSAO with a limit of detection (LOD) of 0.252 ng/mL. Such a nanoprobe was capable of sensitive SSAO detection in the in vitro PD model based on brain biochips, as well as enabling practical analysis of clinical human serum samples. Application of AuNPs@MEA to PD patient serum diagnosis revealed significantly elevated SSAO compared to healthy controls, indicating its high correlation with the pathogenesis of PD (n = 20). This nanoprobe also offered advantages for on-site serological diagnostic needs, such as minuscule sample volume (5 μL), fast response (<5 min), and high-throughput features, exhibiting potential for clinical translations.