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Molecules 2015, 20(7), 13313-13323; doi:10.3390/molecules200713313

Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo

1
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway
2
Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
3
Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0379 Oslo, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 28 April 2015 / Revised: 10 June 2015 / Accepted: 9 July 2015 / Published: 22 July 2015
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
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Abstract

In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface and subsequently endocytosed or actually transported into the cytosol, either by direct plasma membrane penetration or after endocytosis. This discussion includes comments about pitfalls when using pharmacological inhibitors in such studies. The possibility of exploiting CPPs as carriers for the delivery of drugs of different sizes in vitro is discussed, as is the use of CPPs as carriers for therapeutic drugs or contrast agents in vivo. We conclude that in many cases, more studies are needed to demonstrate conclusively whether increased delivery of a substance attached to CPPs is due to a membrane-penetrating property or whether the increase is a consequence of just changing the charge of the substance to be delivered. Finally, the expected dose needed for the use of such conjugates in vivo is discussed, including aspects to consider in order to bring potential products into clinical use. View Full-Text
Keywords: cell-penetrating peptides; cellular uptake; endocytosis; drug delivery; in vivo dose; drug delivery; pharmaceutical development cell-penetrating peptides; cellular uptake; endocytosis; drug delivery; in vivo dose; drug delivery; pharmaceutical development
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MDPI and ACS Style

Skotland, T.; Iversen, T.G.; Torgersen, M.L.; Sandvig, K. Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo. Molecules 2015, 20, 13313-13323.

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