线粒体靶向是解决当前化疗临床应用和多种疾病诊断问题的一种有前途的方法。这里,我们讨论了线粒体靶向部分与抗癌药物的直接缀合,抗氧化剂和传感器分子。其中,应用最广泛的线粒体靶向部分是三苯基鳞(TPP),它是一种离域的阳离子脂质,由于线粒体膜电位高负,因此很容易积累并穿透线粒体膜。其他部分,包括短肽,dequalinium,胍,罗丹明,和F16也已知是有前途的线粒体靶向剂。线粒体靶向部分与抗癌药物的直接缀合,抗氧化剂和传感器导致细胞毒性增加,抗氧化活性和传感活性,分别,与他们的非目标对手相比,尤其是在耐药细胞中。尽管已经在体外和体内研究了许多线粒体靶向的抗癌药物缀合物,仍需进一步的临床研究.另一方面,已经在临床阶段I分析了几种线粒体靶向抗氧化剂,II和III试验,在俄罗斯,一种结合物已被批准用于治疗眼病。有许多正在进行的线粒体靶向传感器的研究。
Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo, further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.