A FRET-Mediated AIE Biosensor Based on Functionalized Peptide-Stabilized Gold Nanoclusters for Sensitive Detection of Matrix Metalloproteinase-2

Matrix metalloproteinase-2 (MMP-2) represents a critical biomarker closely associated with tumor growth, invasion, and metastasis. Herein, we report an ultrasensitive biosensor that integrates Förster resonance energy transfer (FRET) and aggregation-induced emission (AIE) using functionalized peptide-stabilized gold nanoclusters (PG-Au NCs) and Fe 3 O 4 magnetite nanoparticles (MNPs) for the detection of MMP-2. The AIE-type PG-Au NCs are synthesized via a green, simple, one-step approach using functionalized peptide and glutathione as cotemplating ligands. The functionalized peptide is designed to possess both a self-assembling sequence and MMP-2 responsiveness. A FRET system is constructed using PG-Au NCs as energy donors and Fe 3 O 4 MNPs as energy acceptors. MMP-2-mediated specific cleavage releases PG-Au NCs from the Fe 3 O 4 MNPs surface, disrupting the FRET system and restoring PG-Au NCs photoluminescence (PL). Simultaneously, the self-assembled peptides exposed on the surface of PG-Au NCs induce aggregation, triggering AIE and resulting in a further PL enhancement. This one-step triggered dual-PL-enhanced biosensor enables highly sensitive and specific detection of MMP-2 within a range of 1–80 ng/mL, with a detection limit (LOD) of 0.4863 ng/mL. The biosensor has been successfully applied to detect MMP-2 in cancer cell secretions and human serum samples. Furthermore, the FRET-mediated AIE biosensor was integrated into a microfluidic chip for simple and visual detection of MMP-2.