Figure 2.

Cell-penetrating peptide internalization occurs through direct penetration (left) or endocytic pathways (right). Direct translocation of CPPs into the cellular space can occur through energy-independent mechanisms that cause membrane destabilization such as the “carpet-like” model or formation of inverted micelles, or through direct pore formation such as the “barrel-stave” model. The majority of CPPs are thought to be taken up through energy-dependent endocytic internalization either through clathrin-dependent, caveolin-mediated, and clathrin/caveolae independent endocytosis or micropinocytosis before escape from endosome compartments into the cellular environment.