Cancer chemoprevention is the most effective approach to control cancer in the population. Despite significant progress, chemoprevention has not been widely adopted because agents that are safe tend to be less effective and those that are highly effective tend to be toxic. Thus, there is an urgent need to develop novel and effective chemopreventive agents, such as mitochondria-targeted agents, that can prevent cancer and prolong survival. Mitochondria, the central site for cellular energy production, have important functions in cell survival and death. Several studies have revealed a significant role for mitochondrial metabolism in promoting cancer development and progression, making mitochondria a promising new target for cancer prevention. Conjugating delocalized lipophilic cations such triphenylphosphonium cation (TPP+) to compounds of interest is an effective approach for mitochondrial targeting. The hyperpolarized tumor cell membrane and mitochondrial membrane potential allow for selective accumulation of TPP+ conjugates in tumor cell mitochondria versus those in normal cells. This could enhance direct killing of pre-cancerous, dysplastic, and tumor cells while minimizing potential toxicities to normal cells.

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线粒体作为癌症化学预防的新靶点：线粒体靶向剂的出现

癌症化学预防是控制人群癌症的最有效方法。尽管取得了重大进展，但化学预防并未被广泛采用，因为安全的药物往往效果较差，而高效的药物往往有毒。因此，迫切需要开发能够预防癌症和延长生存期的新型有效化学预防剂，例如线粒体靶向剂。线粒体是细胞能量产生的中心部位，在细胞存活和死亡中具有重要作用。几项研究揭示了线粒体代谢在促进癌症发展和进展中的重要作用，使线粒体成为预防癌症的有希望的新靶点。将离域的亲脂性阳离子如三苯基鏻阳离子 (TPP+) 与目标化合物结合是一种有效的线粒体靶向方法。超极化的肿瘤细胞膜和线粒体膜电位允许 TPP+ 缀合物在肿瘤细胞线粒体中的选择性积累，而不是在正常细胞中的那些。这可以增强对癌前细胞、发育不良细胞和肿瘤细胞的直接杀伤，同时最大限度地减少对正常细胞的潜在毒性。