MXene-Enhanced Electrochemiluminescence Biosensor for SERPINE1 Detection via β-Turn-Responsive Peptide as a Functional Biological Macromolecule Switch

Background Electrochemiluminescence (ECL) biosensors are powerful tools for biomarker detection due to high sensitivity, low background, and programmable signal generation. However, conventional ECL platforms face limitations including reliance on static recognition elements (e.g., antibodies) and susceptibility to denaturation. To address this, we developed a novel β-turn-structured peptide-based ECL biosensor integrating MXene (Ti3C2) nanomaterials with a Ru(dcbpy)32+/AuNPs hybrid. This system targets SERPINE1, a senescence-associated secretory protein and promising early biomarker for lung cancer, leveraging peptide conformational switching for enzyme-free signal amplification. Results The biosensor employs a rationally engineered peptide probe containing: (1) a SERPINE1-specific recognition motif, (2) a central β-turn domain locking the peptide in a catalytically inactive folded state, and (3) a His/Cys-rich tail mimicking peroxidase-like activity. Target binding unfolds the β-turn structure, exposing catalytic residues that accelerate tripropylamine (TPA) oxidation and enhance ECL emission. MXene provides a high-conductivity platform while facilitating efficient peptide immobilization via embedded AuNPs. Under optimized conditions, the sensor achieves ultrasensitive detection of SERPINE1 with a wide linear range (0.05–800 ng/mL), a low detection limit (11.2 pg/mL), and high specificity. It operates without enzymatic amplification and demonstrates excellent reproducibility (RSD = 4.2%) and stability (>85% signal retention after 8 days). Validation in human serum yielded recoveries of 96.3–104.6%. Significance This work introduces the first MXene-assisted ECL biosensor utilizing β-turn peptide conformational switching. The enzyme-free, modular strategy offers clinically adaptable detection of senescence biomarkers for early lung cancer diagnosis. By integrating molecular recognition, structural dynamics, and nanomaterial-enhanced signal transduction, this platform advances programmable biosensing and can be extended to other disease-related targets through peptide redesign, showing broad potential in precision diagnostics.