Issue 34, 2019

Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging

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 with 5BMF 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 of 5BMF 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 translating 5BMF into a novel and highly promising DLC for cancer theranostics.

Graphical abstract: Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging

Supplementary files

Article information

Article type
Edge Article
Submitted
22 mar 2019
Accepted
25 iyn 2019
First published
08 iyl 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 7946-7951

Mitochondria-targeting fluorescent molecules for high efficiency cancer growth inhibition and imaging

H. Chen, J. Wang, X. Feng, M. Zhu, S. Hoffmann, A. Hsu, K. Qian, D. Huang, F. Zhao, W. Liu, H. Zhang and Z. Cheng, Chem. Sci., 2019, 10, 7946 DOI: 10.1039/C9SC01410A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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