An Activatable NIR Fluorescent Probe for NAD(P)H and Its Application to the Real-Time Monitoring of p53 Abnormalities In Vivo.

Abstract

NAD(P)H is crucial for biosynthetic reactions and antioxidant functions. However, the current probes developed for detecting NAD(P)H in vivo require intratumoral injection, which limited their application for animal imaging. To address this issue, we have developed a liposoluble cationic probe, KC8, which exhibits excellent tumor-targeting ability and near-infrared (NIR) fluorescence after reaction with NAD(P)H. By using KC8, it was demonstrated for the first time that the level of NAD(P)H in the mitochondria of living colorectal cancer (CRC) cells was highly related to the abnormality of the p53. Furthermore, KC8 was successfully used to differentiate not only between tumor and normal tissue but also between tumors with p53 abnormality and normal tumors when administered intravenously. Finally, we evaluated tumor heterogeneity through two fluorescent channels after treating a tumor with 5-Fu. This study provides a new tool for real-time monitoring of the p53 abnormality of CRC cells.