Abstract.
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.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 30 June 2005; received after revision 9 August 2005; accepted 30 August 2005
Rights and permissions
About this article
Cite this article
Melikov, K., Chernomordik, L.V. Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery. Cell. Mol. Life Sci. 62, 2739–2749 (2005). https://doi.org/10.1007/s00018-005-5293-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-005-5293-y