An Activatable NIR Fluorescent Probe for NAD(P)H and Its Application to the Real‐Time Monitoring of p53 Abnormalities In Vivo. Issue 19 (28th March 2023)

• Record Type: Journal Article
• Authors: Ma, Kaiqing; Yang, He; Wu, Xingkang; Huo, Fangjun; Cheng, Fangqin; Yin, Caixia
• Is Part Of: Angewandte Chemie international edition. Volume 62:Issue 19(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-28
• Subjects: Fluorescent Probe -- NAD(P)H -- NIR -- Tumor Heterogeneity -- p53; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202301518
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : The level of NAD(P)H in mitochondria in living colorectal cancer cells (CRCs) was demonstrated to be highly co‐related to p53 abnormality for the first time by employing a selective NIR fluorescent probe KC8 for NAD(P)H. Due to its NIR emission (745 nm) and excellent tumor‐targeting character, KC8 was enriched in tumor region when administered intravenously, which was further utilized to discriminate the HCT‐116 p53−/− from HCT‐116 in vivo.