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

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 trans...

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Detalles Bibliográficos
Autores principales: Skotland, Tore, Iversen, Tore Geir, Torgersen, Maria Lyngaas, Sandvig, Kirsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332435/
https://www.ncbi.nlm.nih.gov/pubmed/26205056
http://dx.doi.org/10.3390/molecules200713313
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author Skotland, Tore
Iversen, Tore Geir
Torgersen, Maria Lyngaas
Sandvig, Kirsten
author_facet Skotland, Tore
Iversen, Tore Geir
Torgersen, Maria Lyngaas
Sandvig, Kirsten
author_sort Skotland, Tore
collection PubMed
description 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.
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spelling pubmed-63324352019-01-24 Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo Skotland, Tore Iversen, Tore Geir Torgersen, Maria Lyngaas Sandvig, Kirsten Molecules Review 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. MDPI 2015-07-22 /pmc/articles/PMC6332435/ /pubmed/26205056 http://dx.doi.org/10.3390/molecules200713313 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Skotland, Tore
Iversen, Tore Geir
Torgersen, Maria Lyngaas
Sandvig, Kirsten
Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title_full Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title_fullStr Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title_full_unstemmed Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title_short Cell-Penetrating Peptides: Possibilities and Challenges for Drug Delivery in Vitro and in Vivo
title_sort cell-penetrating peptides: possibilities and challenges for drug delivery in vitro and in vivo
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332435/
https://www.ncbi.nlm.nih.gov/pubmed/26205056
http://dx.doi.org/10.3390/molecules200713313
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