Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging. Issue 34 (15th July 2019)

• Record Type: Journal Article
• Authors: Chen, Hao; Wang, Jing; Feng, Xin; Zhu, Mark; Hoffmann, Simon; Hsu, Alex; Qian, Kun; Huang, Daijuan; Zhao, Feng; Liu, Wei; Zhang, Huimao; Cheng, Zhen
• Is Part Of: Chemical science. Volume 10:Issue 34(2019)
• Page Start: 7946
• Page End: 7951
• Publication Date: 2019-07-15
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc01410a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : 5BMF is a new fluorescent mitochondria-accumulating delocalized lipophilic cations [DLC] that boasts significantly increased anti-cancer effects and low toxicity in comparison to previous DLCs, addressing current hurdles in DLC clinical translation. Abstract : Fluorescent mitochondria-accumulating delocalized lipophilic cations (DLCs) for cancer therapy have drawn significant attention in the field of cancer theranostics. One of the most promising fluorescent DLCs, F16, can selectively trigger the apoptosis and necrosis of cancer cells, making it an attractive targeted theranostic drug candidate. However, it suffers from low clinical translation potential, largely due to its inefficient anti-cancer activity (IC50 in the μM range) and poorly understood structure–activity relationship (SAR). In this report, eleven indole-ring substituted F16 derivatives (F16s) were synthesized. Among these derivatives, 5BMF was identified as a highly effective theranostic agent, with in vitro studies showing a low IC50 of ∼50 nM (to H2228 cells) and high cancer to normal cell selectivity index of 225. In vivo studies revealed that tumors treated with5BMF were significantly suppressed (almost no growth over the treatment period) compared to the PBS treated control group, and also no obvious toxicity to mice was found. In addition, the tumor imaging capability of5BMF was demonstrated by in vivo fluorescence imaging. Finally, we report for the first time a proposed SAR for F16 DLCs. Our work lays down a solid foundation for translating5BMF into a novel and highly promising DLC for cancer theranostics.