A universal self-assembled peptide nanoparticle coupled SERS tag in biosensing

Surface-enhanced Raman scattering (SERS) nanotags have been extensively studied for targets detection. However, achieving accurate detection of specific targets often requires the functionalization of SERS nanostructures with various biological components like antibodies, nucleic acid aptamers, or peptides. This process is intricate and involves introducing different functional groups on the protective shell layer, which may result in SERS nanotags aggregation, reduced biorecognition element activity, and chaotic orientation on the surface. In this study, we devised spherical peptide nanoparticles with both recognition and anchoring functions through the self-assembly of TFF and CFF peptides, presenting a versatile strategy for SERS nanotag functionalization. The exposed cysteine residues and T sequences (served as the target-specific recognition sequence) after self-assembly, demonstrated binding to gold SERS nanostructure and recognition of specific targets, respectively. We showcase the high sensitivity and specificity of this method by detecting the liver fibrosis marker LECT2. The method was highly sensitive for the detection of LECT2 with an LOD of 0.0015 ng/mL. The method's adaptability is underscored by the ease of adjusting the sequence within the T portion, suggesting its potential generalization for the efficient detection of various targets.