Ligand-Driven Enzyme-Accelerated Signal Enhancement via Polydopamine Deposition for Visualizing Cell Receptors

Abstract

To address the challenge of faint fluorescence (FL) in cell surface-targeted diagnostics, we propose a ligand-driven enzyme-accelerated signal enhancement (L-EASE) technique through polydopamine (PDA) deposition to clearly visualize cancer cells. Within this framework, aptamers or peptides function as receptor-targeting ligands, and PDA acts as a signal enhancer. Upon exposure to biotinylated ligands, cancer cells underwent the L-EASE reaction involving avidin-conjugated horseradish peroxidase (HRP) and HRP-accelerated dopamine oxidation. This reaction led to rapid PDA deposition, facilitating the binding of amine-functionalized quantum dots near receptors and thereby amplifying the FL signal in cancer cells. Notably, when used with receptor-targeting aptamers and peptides in prostate cancer cells (PC-3) and breast cancer cells (MCF-7), L-EASE significantly enhanced the FL in cancer cells with high specificity, enabling the detection of aptamers or peptides at concentrations 100−1000 times lower than those achievable with traditional FL methods. Our findings suggest the potential of L-EASE as a universal visualization method with exceptional sensitivity and usability for detecting cancer cells and tissues.