Plasmonic Mesoporous Gold‐Based SERS Biosensor for Ovarian Cancer‐Derived Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) are lipids bilayer‐delimited particles carrying bioactive molecules such as proteins, lipids, and nucleic acids, reflecting the physiological state of their origin. Found in biofluids like saliva, urine, blood, and peritoneal fluid, EVs serve as promising minimally invasive biomarkers for several conditions including cancer. However, achieving high sensitivity and specificity in EV detection remains technically challenging. Placental Alkaline Phosphatase (PLAP), an enzyme primarily expressed in the placenta during pregnancy, has emerged as a clinically relevant biomarker in gynecological malignancies, including ovarian cancer (OC). In this study, a nanoengineered mesoporous gold (mAu)‐based Surface‐Enhanced Raman Spectroscopy (SERS) platform is reported for the rapid and ultrasensitive detection of PLAP‐positive EVs in OC patients. The mAu offers high surface roughness, enabling numerous localized plasmonic hotspots that amplify Raman signals and improve probe and antibody loading. This allowed the detection of as few as 100 EVs mL⁻¹ with excellent reproducibility (RSD < 5%,n = 3). In clinical validation (n = 30), the assay achieved 90% sensitivity (95% CI: 60%–100%) and 85% specificity (95% CI: 15%–100%) in distinguishing OC patients from those with benign and healthy controls, demonstrating superior performance compared to CA‐125. The mAu‐SERS platform shows considerable promise as a minimally invasive and clinically applicable diagnostic strategy for OC, especially for differential diagnosis for their ability to distingluis between benign and OC conditions.