The abnormal expression of N-acetylneuraminic acid (SA) and sialylated glycoproteins in biological fluids are closely associated with various diseases including cancer. However, the low content of SA and the strong interference of complex matrix greatly influence the effective capture of SA in biosamples prior to analysis. Herein, a dual-capture-system strategy based on molecular imprinting and post-imprinting modification (PIM) was proposed to precisely capture SA with improved binding affinity and specificity. After imprinting with SA as template, dynamic imine bonds are introduced by post-imprinting modification, enabling sufficiently high specificity to capture SA through imprinting cavities and the dynamic imine bonds hydrolysis reaction simultaneously. The prepared magnetic PIM polymers (Mag-MIPs-PIM) exhibited significantly high specificity both for SA (IF = 4.24) and sialylated glycoprotein (IFTRF = 3.50). In addition, the feasibility of Mag-MIPs-PIM for practical application was demonstrated by association with HPLC for the determination of SA in human serum, and an LOD of 0.01 × 10−2 g L−1 was obtained. The proposed strategy based on molecular imprinting and PIM provides a new inspiration for the improvement of selectivity of the molecularly imprinted polymers.
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