Development of a europium–salicylic acid based nano-biosensor for early detection of GPC3 in DEN-induced hepatocellular carcinoma

The early diagnosis of hepatocellular carcinoma (HCC) is hindered by a lack of highly sensitive and specific biomarkers. This study addresses this challenge by developing a novel optical biosensor targeting Glypican-3 (GPC3), a promising biomarker for HCC. A luminescent europium-salicylic acid (Eu-SA) complex was synthesized via a sol-gel method and embedded in an epoxy-methyl cellulose thin film to create a low-cost sensing platform. Molecular docking confirmed the superior binding affinity of the Eu-SA complex to the GPC3 antibody interface over samarium or terbium analogues. The fabricated biosensor exhibited characteristic excitation and emission peaks at 395 nm and 618 nm, respectively. After antibody functionalization, it demonstrated a linear response to GPC3 from 0.01 to 0.167 ng/mL (Y = -0.968 + 45.36x, r = 0.97), with a detection limit of 0.159 ng/mL. The biosensor was biologically validated using serum from diethylnitrosamine (DEN)-induced HCC mice, showing excellent diagnostic performance with a 0.93 correlation to ELISA and an area under the curve (AUC) of 0.96. These results establish the Eu-SA thin-film biosensor as a sensitive, selective, and affordable tool for GPC3 detection, holding strong potential for point-of-care early HCC diagnostics.