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. 2009 Mar 20;157(2):195–206. doi: 10.1111/j.1476-5381.2009.00057.x

Figure 1.

Figure 1

Model of cellular uptake and intracellular trafficking of cell-penetrating peptides (CPPs). Cellular uptake of CPP by the covalent (CPP-CS) and non-covalent (CPP-NCS) strategies. (1) Binding of CPPs or CPP/cargo complexes to extracellular matrix via the cell surface proteoglycan platform, (2) clustering of GlucosAminoGlycan platform triggers selective activation of small GTPase and remodelling of the actin network, (3) increase of membrane fluidity or microdomain dynamic promotes the cell entry and release in the cytosol of CPP-NCS and of CPP-CS (at high concentrations) via membrane fusion or cellular uptake of CPP-CS/CPP-NCS via (4) endocytosis pathway (a: caveolin-dependent, b: clathrin-dependent, c: clathrin-and caveolin-independent) or (5) macropinocytosis. After endocytic capture, CPP-CS can escape from lysosomal degradation and enter the cytosol and the nucleus (6), remain in the early or late endosomes (7), or be delivered in the Golgi apparatus and the endoplasmic reticulum (8).