Quantification of Single‐Cell Cysteine Using an Electrochemical Nanosensor for Predicting Tumor Disulfidptosis Susceptibility

ABSTRACT Disulfidptosis, a newly identified form of programmed cell death, has emerged as a promising therapeutic target for tumors. However, the current research in this field is hindered by the absence of precise and quantifiable biomarkers to accurately predict and monitor its occurrence and progression. Research has demonstrated a strong correlation between disulfidptosis and cysteine metabolism. To elucidate the relationship, this study pioneers the development of a novel carbon fiber nanoelectrode (CFNE) enhanced with platinum nanoparticles and poly(p‐coumaric acid) (PPCA) for precise cysteine detection in living single‐cells, thereby overcoming cellular heterogeneity. The nanosensor reveals that the increased original intracellular cysteine production levels, particularly those exceeding 400 amol s ⁻¹ , serve as a reliable predictor of high susceptibility to disulfidptosis. The relationship between the cell signaling pathway of cysteine metabolism with disulfidptosis is demonstrated by the nanosensor, which is further substantiated through a comprehensive analysis of diverse tumor cell lines and primary tumor cells in a mouse model. This study proposes a new indicator of disulfidptosis, and the developed nanosensor is poised to become an indispensable tool for both disulfidptosis research and the evaluation of tumor therapeutic strategies.