Mitochondrial Targeting Peptide-based Nanodelivery for Cancer Treatment

Abstract

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.

Keywords: Cancer treatment; liposomes; mitochondria; nanodelivery; targeted peptides; tumor.