Cell-penetrating peptides (CPPs) have the ability to enter a cell’s plasma membrane independent of a membrane receptor. Attached to a CPP, therapeutic cargo could be delivered to an intracellular target, thus overcoming the entry restrictions set by the plasma membrane.
The cationic CPPs interact with negatively charged head groups of lipids directly in the plasma membrane through electrostatic interactions. The increased local peptide concentration at the membrane surface will cause a transient destabilization of the lipid bilayer and lead to cell entry. The hydrophobic interactions, especially facilitated by the presence of tryptophan residues, may be important for the CPP-membrane interaction and cellular internalization.
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