Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

Abstract

Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

Keywords: cancer; cell-penetrating-peptides; protein transduction domains.

Figure 1

CPP translocation mechanisms.

Figure 2

Strategies for tumor-specific CPP-conjugate delivery. To further enhance CCP-mediated intracellular uptake of conjugates, cargos can be linked to either tumor-homing CPPs (A), tumor-homing moiety (B) or membrane receptor specific antibody (C). Moreover, CPP-based drugs can be designed so they are only activated in the close neighborhood of tumor, where the microenvironment is different (D) or inside the transformed cell (E).