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Membranotropic Cell Penetrating Peptides: The Outstanding Journey

Department of Pharmacy, University of Naples “Federico II”, Via Mezzocannone 16, 80134 Naples, Italy
CiRPEB, University of Naples “Federico II”, Via Mezzocannone 16, 80134 Naples, Italy
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy
Author to whom correspondence should be addressed.
Academic Editor: Jagdish Singh
Int. J. Mol. Sci. 2015, 16(10), 25323-25337;
Received: 18 September 2015 / Revised: 30 September 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
(This article belongs to the Special Issue Cell-Penetrating Peptides)
PDF [753 KB, uploaded 23 October 2015]


The membrane bilayer delimits the interior of individual cells and provides them with the ability to survive and function properly. However, the crossing of cellular membranes constitutes the principal impediment to gaining entry into cells, and the potential therapeutic application of many drugs is predominantly dependent on the development of delivery tools that should take the drug to target cells selectively and efficiently with only minimal toxicity. Cell-penetrating peptides are short and basic peptides are widely used due to their ability to deliver a cargo across the membrane both in vitro and in vivo. It is widely accepted that their uptake mechanism involves mainly the endocytic pathway, the drug is catched inside endosomes and lysosomes, and only a small quantity is able to reach the intracellular target. In this wide-ranging scenario, a fascinating novel hypothesis is that membranotropic peptides that efficiently cross biological membranes, promote lipid-membrane reorganizing processes and cause a local and temporary destabilization and reorganization of the membrane bilayer, may also be able to enter cells circumventing the endosomal entrapment; in particular, by either favoring the escape from the endosome or by direct translocation. This review summarizes current data on membranotropic peptides for drug delivery. View Full-Text
Keywords: membranotropic peptides; hydrophobicity; fusion; delivery membranotropic peptides; hydrophobicity; fusion; delivery

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Falanga, A.; Galdiero, M.; Galdiero, S. Membranotropic Cell Penetrating Peptides: The Outstanding Journey. Int. J. Mol. Sci. 2015, 16, 25323-25337.

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