A Magnetic Colorimetric Aptasensor Based on Fe3O4@CQDs Nanocomposites for Ultrasensitive Detection of Glypican-3

Hepatocellular carcinoma (HCC) remains one of the most lethal malignancies worldwide, underscoring the urgent demand for early diagnostic strategies to improve patient survival rates. Glypican-3 (GPC3), a highly specific biomarker of HCC, has emerged as a promising target for early detection. Herein, we developed an innovative magnetic colorimetric aptasensor using ferrosoferric oxide@carbon quantum dots (Fe₃O₄@CQDs) nanocomposites. The Fe₃O₄@CQDs nanocomposites combine the magnetic properties of Fe₃O₄ with the unique optical characteristics of CQDs, exhibiting intrinsic peroxidase‑like activity. The animo-modified GPC3 aptamer (GPC3_Apt) was covalently conjugated onto the Fe₃O₄@CQDs nanocomposites surface via EDC/NHS chemistry to form the recognition probe (Fe₃O₄@CQDs-GPC3_Apt). Upon specific binding between the aptamer and GPC3, the resulting complexes (Fe₃O₄@CQDs-GPC3_Apt-GPC3) modulate the catalytic oxidation of o-phenylenediamine (OPD) by H₂O₂, generating a yellow oxOPD product whose absorbance intensity correlated with GPC3 concentration. The proposed colorimetric aptasensor demonstrated a detection limit of 3.16 ng/mL and a linear range of 10–200 ng/mL, with high specificity against interfering proteins. It was successfully validated in human serum samples, yielding recoveries between 99.27% and 109.33%. Owing to its operational simplicity and cost‑effectiveness, this platform offers transformative potential for point-of-care HCC screening. Beyond advancing GPC3 detection, the work provides a flexible design paradigm that can be adapted for assays targeting other disease biomarkers.