Peptide-Conjugated Dual-Photoelectrode Platform for Enhanced Anti-Interference Photoelectrochemical Cytosensing

Accurate probing of circulating tumor cells (CTCs) is critical for early cancer diagnosis and effective clinical intervention. However, achieving reliable cytosensing in complex biological fluids remains an arduous endeavor due to issues such as biooxidation and nonspecific biofouling, particularly at trace levels of CTCs. In this work, we present a novel, robust anti-interference photoelectrochemical (PEC) cytosensing strategy by integrating a peptide conjugation approach into a dual-photoelectrode platform. The system features a TiO₂/SCN photoanode and a PEDOT/Pt photocathode connected in series, functioning as a signal transducer to generate a distinct photocurrent response. A conjugate comprising an antifouling peptide (Pep) and a cell-specific aptamer (Apt) was constructed via bio-orthogonal click chemistry. This Pep-Apt bioconjugate was immobilized onto the photocathode, where the Pep domain forms a hydration barrier to suppress nonspecific protein adsorption, while the Apt domain facilitates selective recognition and capture of target cells. The synergistic integration of the dual-photoelectrode architecture with the peptide conjugation strategy not only imparts excellent antifouling performance but also simplifies surface functionalization. Using HepG2 cells as a model for hepatocellular carcinoma, the developed PEC cytosensor exhibited high sensitivity, strong selectivity, and robust anti-interference capability, underscoring its potential for clinical translation.