Tumor recurrence as a result of therapy-induced nuclear DNA lesions is a major issue in cancer treatment. Currently, only a few examples of potentially non-genotoxic drugs have been reported. Mitochondrial re-localization of ciprofloxacin, one of the most commonly prescribed synthetic antibiotics, is reported here as a new approach. Conjugation of ciprofloxacin to a triphenyl phosphonium group (giving lead Mt-CFX) is used to enhance the concentration of ciprofloxacin in the mitochondria of cancer cells. The localization of Mt-CFX to the mitochondria induces oxidative damage to proteins, mtDNA, and lipids. A large bias in favor of mtDNA damage over nDNA was seen with Mt-CFX, contrary to classic cancer chemotherapeutics. Mt-CFX was found to reduce cancer growth in a xenograft mouse model and proved to be well tolerated. Mitochondrial re-localization of antibiotics could emerge as a useful approach to generating anticancer leads that promote cell death via the selective induction of mitochondrially mediated oxidative damage.

由治疗引起的核DNA损伤导致的肿瘤复发是癌症治疗中的主要问题。目前，仅报道了少数非遗传毒性药物的例子。据报道，环丙沙星是最常用的合成抗生素之一，线粒体重新定位是一种新方法。环丙沙星与三苯基phospho基团的结合（产生的前导Mt-CFX）可用于增强癌细胞线粒体中环丙沙星的浓度。Mt-CFX定位于线粒体会诱导对蛋白质，mtDNA和脂质的氧化损伤。与经典的癌症化学疗法相反，在Mt-CFX上发现mtDNA损伤比nDNA损伤大。在异种移植小鼠模型中发现Mt-CFX可减少癌症的生长，并被证明具有良好的耐受性。