Peptides containing blocks of different charge densities facilitate cell uptake of oligonucleotides

Physical Chemistry Chemical Physics : PCCP
Jihan ZhouDehai Liang

Abstract

Polyelectrolyte complexes (PECs) are of great importance in drug delivery and gene therapy. The density and the distribution of the charges are key parameters of a polyelectrolyte, determining the structure of the complex and the kinetics of the complexation. Using peptides of precisely-controlled charge density as model molecules, we showed that the presence of weakly-charged peptides, (KGGG)5 or (KGKG)5, did not affect the complexation of highly-charged peptides (KKKK)5 with 21 bp oligonucleotides. However, peptide containing blocks of different charge densities, such as (KKKK)5-b-(KGGG)5 or (KKKK)5-b-(KGKG)5, exhibited superior performance during complexation. With a relatively uniform small size, the complex was also stable in serum. More importantly, the cellular uptake of the complex was greatly enhanced by a ratio of 40-60%, compared to that of the complex formed by uniformly-charged peptides. We attributed the improvement to the structure of the complex, in which the highly-charged blocks form the core with the oligonucleotide whilst the weakly-charged blocks dangle outside, preventing the complexes from further aggregation.

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P L FelgnerM Danielsen
Jul 9, 1999·Reviews in Medical Virology·N E Bishop
Jan 18, 2003·Journal of Pharmaceutical Sciences·Christopher M Wiethoff, C Russell Middaugh
Mar 7, 2003·Gene Therapy·H Herweijer, J A Wolff
Aug 7, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Dirk LochmannAndreas Zimmer
Apr 20, 2005·The Journal of Chemical Physics·A Fernández-Nieves, M Márquez
Nov 15, 2005·Biomacromolecules·Elizabeth S TrukhanovaAlexander N Zelikin
Mar 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Julie A Champion, Samir Mitragotri
Apr 6, 2006·Langmuir : the ACS Journal of Surfaces and Colloids·Jérôme F L Duval, Hiroyuki Ohshima
Jan 26, 2007·Pharmaceutical Research·Weijun Li, Francis C Szoka
Jun 6, 2008·Gene Therapy·D Schaffert, E Wagner
Sep 11, 2008·Nature Reviews. Genetics·Michele A Kutzler, David B Weiner
Dec 5, 2008·Chemical Reviews·Meredith A Mintzer, Eric E Simanek
Jan 1, 2009·Molecular Pharmaceutics·Kun Gao, Leaf Huang
Jan 23, 2009·Nature·Daniela Castanotto, John J Rossi
Jan 31, 2009·Nature Reviews. Drug Discovery·Kathryn A WhiteheadDaniel G Anderson
May 9, 2009·Advanced Drug Delivery Reviews·Younsoo Bae, Kazunori Kataoka
Oct 31, 2009·International Journal of Pharmaceutics·Soma PatnaikK C Gupta
May 8, 2010·Chemical Society Reviews·Ramishetti SrinivasArabinda Chaudhuri
Mar 6, 2012·Chemical Society Reviews·Irene Canton, Giuseppe Battaglia
Jun 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Poornima KolharSamir Mitragotri
Feb 4, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Ann K NowinskiShaoyi Jiang

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Citations

Aug 16, 2017·Physical Chemistry Chemical Physics : PCCP·Wei PanDehai Liang

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