mtDNA-triggered pH response signal-amplified fluorescent probe for multiple cell discrimination

Developing fluorescence probes with multiple responses has vital significance but remains challenging. Herein, for the first time, we present a mitochondrial DNA (mtDNA)-triggered pH response signal-amplified fluorescent probe (QCY-DBT) for multiple cell detection. The probe exhibited a large stokes shift (229 nm), excellent DNA selectivity over RNA, and ultrasensitivity of detection limit (DL; 74.0 ng/mL). Thus, QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic cells. In the tumor acidic environment (pH 6.0–7.0), the absorbance of QCY-DBT at 436 nm increased, and the fluorescence signal (665 nm) was amplified by mtDNA, which enabled the direct observation of tumor cells. Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.