SERS-Nanozyme Cooperative Ag@Lacunary-POM Nanoclusters for Exosome Biosensing

The detection of cancer-related exosomes is of great significance for the early diagnosis of cancer and the prediction of prognosis. We developed a SERS-based nanozyme-linked immunosorbent assay (NELISA) utilizing lacunary polyoxometalate Na₇PW₁₁O₃₉, whose vacancy-induced unsaturated coordination sites enhance Lewis/Brønsted acidity and modulate HOMO-LUMO levels. This electronic restructuring synergizes with Ag nanoparticles (NPs) synthesized via NaBH₄ reduction to form Ag@Na₇PW₁₁O₃₉, integrating dual SERS enhancement (LOD: 1.66 × 10^-8 M for 4-MBA) and peroxidase-like catalysis via localized surface plasmon resonance (LSPR) and interfacial charge transfer (CT). CD₉ antibody-functionalized Ag@Na₇PW₁₁O₃₉ selectively captures the exosome through CD₉ transmembrane proteins on microplates. Clinical validation with ovarian/breast cancer patient sera revealed a linear correlation between SERS intensity and exosome concentration (9 × 10⁵-1.78 × 10⁸ particles/mL, LOD: 7.73 × 10⁵ particles/mL), with signals significantly elevated versus healthy controls. The lacunary POM architecture amplifies plasmon-catalytic synergy while enabling direct biointerface engineering. This NELISA-SERS platform achieves noninvasive, ultrasensitive cancer detection, advancing precision diagnostics and early screening paradigms.