Application of cationic cell-penetrating peptides to the intratumoral targeted delivery of breast cancer therapeutics

Abstract

Breast cancer is one of the leading causes of cancer related deaths among women worldwide. Due to the significance and prevalence of this disease, novel therapeutics have recently been explored due to conventional breast cancer therapy having numerous limitations, including multi-drug resistance and extensive off-target side effects. Cell-penetrating peptide-based drug delivery systems are among these therapies and have recently started to undergo clinical trials, hypothesized to hit markets in the near future upon approvals. While these peptides confer their own challenges and limitations, they do offer the promise of high selectivity and specificity in terms of drug delivery due to their ability to cross biological membranes. The majority of these peptides can be characterized as cationic, including the three well known cationic cell-penetrating peptides examined within this review: HIV TAT, penetratin, and polyarginine. Based off the current knowledge of these peptides, including their primary and secondary structures as well as their mechanisms of internalization, several modifications can be made to the peptides in order to increase their efficiency of internalization as well as conjugated drug delivery. Moreover, in terms of breast cancer specifically, modifications can be made to the drug delivery system in order to exploit the breast tumor microenvironment as well as target specific tumor molecular targets, as will be further discussed. Overall, while cell-penetrating peptide based therapies offer great promise to drug therapy, continued and more extensive research is necessary to fully understand the rapidly expanding field.