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Journal of Biophysics
Volume 2011 (2011), Article ID 414729, 10 pages
Review Article

Mechanisms of Cellular Uptake of Cell-Penetrating Peptides

1Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, 10691 Stockholm, Sweden
2Department of Neurochemistry, Arrhenius Laboratories for Natural Sciences, Stockholm University, 10691 Stockholm, Sweden
3Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

Received 24 November 2010; Accepted 24 January 2011

Academic Editor: Eaton Edward Lattman

Copyright © 2011 Fatemeh Madani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recently, much attention has been given to the problem of drug delivery through the cell-membrane in order to treat and manage several diseases. The discovery of cell penetrating peptides (CPPs) represents a major breakthrough for the transport of large-cargo molecules that may be useful in clinical applications. CPPs are rich in basic amino acids such as arginine and lysine and are able to translocate over membranes and gain access to the cell interior. They can deliver large-cargo molecules, such as oligonucleotides, into cells. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms, a subject still under debate. Unresolved questions include the detailed molecular uptake mechanism(s), reasons for cell toxicity, and the delivery efficiency of CPPs for different cargoes. Here, we give a review focused on uptake mechanisms used by CPPs for membrane translocation and certain experimental factors that affect the mechanism(s).