Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 43, 2018
Previous Article Next Article

A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells

Author affiliations

Abstract

One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have significant advantages as gene delivery vehicles by virtue of non-natural ε-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for the potential clinical application of CPs. In a further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particularly LTP, an arginine-rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5–LTP/siRNA complexes have a reasonable tropism to lung tissues.

Graphical abstract: A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells

Back to tab navigation

Supplementary files

Article information


Submitted
20 Aug 2018
Accepted
12 Oct 2018
First published
13 Oct 2018

Org. Biomol. Chem., 2018,16, 8181-8190
Article type
Paper

A novel peptide dendrimer LTP efficiently facilitates transfection of mammalian cells

K. V. Kozhikhova, S. M. Andreev, I. P. Shilovskiy, A. V. Timofeeva, A. R. Gaisina, A. A. Shatilov, E. A. Turetskiy, I. M. Andreev, V. V. Smirnov, A. S. Dvornikov and M. R. Khaitov, Org. Biomol. Chem., 2018, 16, 8181
DOI: 10.1039/C8OB02039F

Social activity

Search articles by author

Spotlight

Advertisements