Classes of Cell-Penetrating Peptides.

During the three decades of cell-penetrating peptides era the superfamily of CPPs has rapidly expanded, and the quest for new sequences continues. CPPs have been well recognized by scientific community and they have been used for transduction of a wide variety of molecules and particles into cultured cells and in vivo. In parallel with application of CPPs for delivering of active payloads, the mechanisms that such peptides take advantage of for gaining access to cells' insides have been in the focus of intense studies. Although the common denominator "cell penetration" unites all CPPs, the interaction partners on the cell surface, evoked cellular responses and even the uptake mechanisms might greatly vary between different peptide types. Here we present some possibilities for classification of CPPs based on their type of origin, physical-chemical properties, and the extent of modifications and design efforts. We also briefly analyze the internalization mechanisms with regard to their classification into groups based on physical-chemical characteristics.