Qingnan Zhao, Saizhen Hu, Wang Fan, Feng Lin, Bing Zhao, Wei Song
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 Na 7 PW 11 O 39, 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 NaBH 4 reduction to form Ag@Na 7 PW 11 O 39, 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). CD 9 antibody-functionalized Ag@Na 7 PW 11 O 39 selectively captures the exosome through CD 9 transmembrane proteins on microplates. Clinical validation with ovarian/breast cancer patient sera revealed a linear correlation between SERS intensity and exosome concentration (9 × 10 5 –1.78 × 10 8 particles/mL, LOD: 7.73 × 10 5 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.