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Int. J. Mol. Sci. 2015, 16(8), 19518-19536; doi:10.3390/ijms160819518

Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the Combination Strategies

2,* and 3,*
Department of Basic Medical Science, Huzhou University School of Medicine, Huzhou 313000, China
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
Moores Cancer Center, University of California San Diego, La Jolla, CA 92093-0820, USA
Authors to whom correspondence should be addressed.
Academic Editor: Jagdish Singh
Received: 21 May 2015 / Revised: 11 July 2015 / Accepted: 30 July 2015 / Published: 18 August 2015
(This article belongs to the Special Issue Cell-Penetrating Peptides)
View Full-Text   |   Download PDF [1468 KB, uploaded 18 August 2015]   |  


Cell-penetrating peptides (CPPs) can cross cellular membranes in a non-toxic fashion, improving the intracellular delivery of various molecular cargos such as nanoparticles, small molecules and plasmid DNA. Because CPPs provide a safe, efficient, and non-invasive mode of transport for various cargos into cells, they have been developed as vectors for the delivery of genetic and biologic products in recent years. Most common CPPs are positively charged peptides. While delivering negatively charged molecules (e.g., nucleic acids) to target cells, the internalization efficiency of CPPs is reduced and inhibited because the cationic charges on the CPPs are neutralized through the covering of CPPs by cargos on the structure. Even under these circumstances, the CPPs can still be non-covalently complexed with the negatively charged molecules. To address this issue, combination strategies of CPPs with other typical carriers provide a promising and novel delivery system. This review summarizes the latest research work in using CPPs combined with molecular cargos including liposomes, polymers, cationic peptides, nanoparticles, adeno-associated virus (AAV) and calcium for the delivery of genetic products, especially for small interfering RNA (siRNA). This combination strategy remedies the reduced internalization efficiency caused by neutralization. View Full-Text
Keywords: cell-penetrating peptides (CPPs); TAT peptide; liposome; nanoparticles; combination delivery; calcium cell-penetrating peptides (CPPs); TAT peptide; liposome; nanoparticles; combination delivery; calcium

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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. (CC BY 4.0).

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Li, H.; Tsui, T.Y.; Ma, W. Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the Combination Strategies. Int. J. Mol. Sci. 2015, 16, 19518-19536.

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