Cell-Penetrating Peptides, Electroporation, and Drug Delivery

Certain short polycations, such as TAT and oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a mechanism called transduction, as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) can carry with them cargos of 30 amino acids, more than the nominal limit of 500 Da and enough to be therapeutic. An analysis of the electrostatics of a charge outside the cell membrane and some recent experiments suggest that transduction may proceed by molecular electroporation. Ways to target diseased cells, rather than all cells, are discussed.