Peptides containing blocks of different charge densities facilitate cell uptake of oligonucleotides.
Phys Chem Chem Phys
; 17(14): 8653-9, 2015 Apr 14.
Article
em En
| MEDLINE
| ID: mdl-25735601
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Fragmentos de Peptídeos
/
Polímeros
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article