*5.2.2.4 Escape from endosomes*

Endocytosis of CPPs happens in two stages as endocytic entry and endosomal escape. Endosomal escape is a major step to prevent disruption of the cargo in the lysosomes and to allow the cargo to reach the extra-endosomal aim and to achieve its biological activity. Several models have been proposed to prevent endosomal escapes of CPPs. For instance, as a result of the electrical interaction between the negative charges of the endosomal membrane and the positively charged parts of the CPPs, the membrane that triggers the release of the vesicle content leads to stiffing and rupture. According to the other example, reduced pH develops the capability of CPPs to attach to the endosomal membrane and then raises intracellular circulation; as a result of which, the increment of endocytic vesicles may ensure better escape from the endosomal membrane [93, 95].
