A novel electrochemical sensor based on Co,N co-doped porous carbon nanocage-carbon nanotube composites for real-time electrochemical monitoring of hydrogen peroxide release in cancer cells.

Hydrogen peroxide (H₂O₂), a key reactive oxygen species (ROS) in vivo, plays an important role in host immune defense against pathogen invasion. Abnormal H2O2 levels are associated with various diseases; therefore, accurate and real-time detection of H2O2 is of considerable biomedical relevance. In this study, a composite material consisting of Co,N co-doped porous carbon nanocages (Co,N-PC) and carbon nanotubes (CNTs) was fabricated and exhibited superior electrocatalytic performance toward H2O2 reduction compared with Co,N-PC without CNTs. The synergistic interaction between CNTs and Co,N-PC enhanced the electrical conductivity and electrochemically active surface area of Co,N-PC@CNTs, thereby improving its electrocatalytic activity and non-enzymatic electrochemical sensing performance toward H2O2. Under optimal conditions, the Co,N-PC@CNTs-modified rotating disk electrode (RDE) exhibited a wide linear concentration range of 0.005-9.5 mM, a high sensitivity of 460.245 μA·mM-1·cm-2, and a low detection limit of 0.060 μM (S/N = 3). Its overall analytical performance surpassed that of the state-of-the-art ZIF-67-derived carbon sensors reported in the literature. Density functional theory (DFT) calculations demonstrated that the introduction of CNTs in conjunction with Co,N-PC effectively modulated the electronic structure and optimized the d-band center, thereby reducing the Gibbs free energy of the rate-determining step, lowering the reaction energy barrier, and accelerating the reaction kinetics. In addition, the sensor exhibited a measurable electrochemical response to H2O2 associated with PMA-stimulated HT29 cells. Therefore, the Co,N-PC@CNTs/RDE sensor provides a promising platform for sensitive H2O2 detection, with potential applications in biological, food, and environmental analysis.