Kansas State University, Department of Chemistry, Manhattan, KS 66506, USA.
The University of Kansas Medical Center, Cancer Biology, Kansas City, KS 66160, USA.
Curr Protein Pept Sci. 2022;23(10):657-671. doi: 10.2174/1389203723666220520160435.
Mitochondria are important intracellular organelles because of their key roles in cellular metabolism, proliferation, and programmed cell death. The differences in the structure and function of the mitochondria of healthy and cancerous cells have made mitochondria an interesting target for drug delivery. Mitochondrial targeting is an emerging field as the targeted delivery of cytotoxic payloads and antioxidants to the mitochondrial DNA is capable of overcoming multidrug resistance. Mitochondrial targeting is preferred over nuclear targeting because it can take advantage of the distorted metabolism in cancer. The negative membrane potential of the inner and outer mitochondrial membranes, as well as their lipophilicity, are known to be the features that drive the entry of compatible targeting moiety, along with anticancer drug conjugates, towards mitochondria. The design of such drug nanocarrier conjugates is challenging because they need not only to target the specific tumor/cancer site but have to overcome multiple barriers as well, such as the cell membrane and mitochondrial membrane. This review focuses on the use of peptide-based nanocarriers (organic nanostructures such as liposomes, inorganic, carbon-based, and polymers) for mitochondrial targeting of the tumor/cancer. Both in vitro and in vivo key results are reported.
线粒体是重要的细胞内细胞器,因为它们在细胞代谢、增殖和程序性细胞死亡中起着关键作用。健康细胞和癌细胞中线粒体的结构和功能的差异使得线粒体成为药物输送的一个有趣的靶点。线粒体靶向是一个新兴的领域,因为将细胞毒性有效载荷和抗氧化剂靶向递送至线粒体 DNA 能够克服多药耐药性。与核靶向相比,线粒体靶向是首选,因为它可以利用癌症中的代谢紊乱。众所周知,内外线粒体膜的负膜电位及其亲脂性是促使相容靶向部分以及抗癌药物偶联物进入线粒体的特征。此类药物纳米载体偶联物的设计具有挑战性,因为它们不仅需要靶向特定的肿瘤/癌症部位,而且还需要克服多个障碍,如细胞膜和线粒体膜。本综述重点介绍了基于肽的纳米载体(有机纳米结构,如脂质体、无机、基于碳的和聚合物)在肿瘤/癌症线粒体靶向中的应用。报告了体外和体内的关键结果。