Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery.
Delivery of macromolecules into living cells by arginine-rich cell penetrating peptides (AR-CPPs) is an important new avenue for the development of novel therapeutic strategies. However, to date the mechanism of this delivery remains elusive. Recent data implicate endocytosis in the internalization of AR-CPPs and their macromolecular cargo and also indicate limited delivery of macromolecules into the cell cytoplasm and nucleus. Different types of endocytosis - clathrin-dependent endocytosis, raft/caveolin-dependent endocytosis and macropinocytosis - are all implicated in the uptake of AR-CPPs and their cargo into different cells. Cationic AR-CPPs dramatically increase uptake of conjugated molecules through efficient binding to surface proteoglycans. Whether this increase in binding can assure delivery of a sufficient amount of functionally active macromolecules into the cytoplasm and nucleus or whether there is a specific mechanism by which AR-CPPs facilitate the escape of conjugated cargo from endosomes remains to be understood.
Melikov
K
K
Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Bldg.10/Rm.10D05, 10 Center Drive, Bethesda, MD 20892-1855, USA. melikovk@mail.nih.gov
Chernomordik
L V
LV
D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008567:Membranes, Artificial; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011956:Receptors, Cell Surface / Q000378:metabolism
D008567:Membranes, Artificial; D010455:Peptides; D011956:Receptors, Cell Surface; D001120:Arginine