G-Quadruplex aptamer–nanoparticle platform for sensitive cytosensing of hepatocellular carcinoma

A rapid and sensitive aptamer-based detection platform for hepatocellular carcinoma (HCC) cells is developed in this study. The sensing strategy utilizes gold nanoparticles (AuNPs) as signal transducers, which exhibit excellent colloidal stability and a characteristic surface plasmon resonance peak at 520 nm under dispersed conditions. Upon the introduction of sodium chloride (NaCl), electrostatic screening weakens nanoparticle stability and induces salt-triggered aggregation. The AS1411 aptamer initially adsorbs onto the AuNP surface, conferring resistance to salt-induced aggregation. In the presence of HepG2 cells, the aptamer preferentially binds to cell-surface targets and undergoes G-quadruplex formation, resulting in desorption from the AuNP surface and subsequent nanoparticle aggregation that enables target recognition. The proposed platform exhibits a significantly enhanced response toward HepG2 cells compared with various normal human cell lines, demonstrating high selectivity. Quantitative analysis reveals a broad logarithmic linear detection range from 1.0 × 101 to 1.0 × 105 cells/mL, with a low limit of detection of 5 cells/mL. Overall, this work establishes a simple, label-free, and enrichment-free cytosensing strategy for tumor cell detection and highlights its potential biomedical diagnostic applications.