Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake

Valeria Márquez-Miranda, Juan Pablo Peñaloza, Ingrid Araya-Durán, Rodrigo Reyes, Soledad Vidaurre, Valentina Romero, Juan Fuentes, Francisco Céric, Luis Velásquez, Fernando D. González-Nilo, Carolina Otero

Resultado de la investigación: Contribución a la publicaciónArticle

  • 8 Citas

Resumen

Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.

IdiomaEnglish
Número de artículo66
Páginas1-13
Número de páginas13
PublicaciónNanoscale Research Letters
Volumen11
Número de edición1
DOI
EstadoPublished - 1 dic 2016

Huella dactilar

Dendrimers
oligonucleotides
Antisense Oligonucleotides
Oligonucleotides
dendrimers
Complexation
cells
DNA
deoxyribonucleic acid
Molecules
plasmids
Single-Stranded DNA
interactions
Cell membranes
Cytotoxicity
activity (biology)
Bioactivity
Scaffolds
Hydroxyl Radical
Functional groups

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics

Citar esto

Márquez-Miranda, V., Peñaloza, J. P., Araya-Durán, I., Reyes, R., Vidaurre, S., Romero, V., ... Otero, C. (2016). Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. Nanoscale Research Letters, 11(1), 1-13. [66]. DOI: 10.1186/s11671-016-1260-9
Márquez-Miranda, Valeria ; Peñaloza, Juan Pablo ; Araya-Durán, Ingrid ; Reyes, Rodrigo ; Vidaurre, Soledad ; Romero, Valentina ; Fuentes, Juan ; Céric, Francisco ; Velásquez, Luis ; González-Nilo, Fernando D. ; Otero, Carolina. / Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. En: Nanoscale Research Letters. 2016 ; Vol. 11, N.º 1. pp. 1-13
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Márquez-Miranda, V, Peñaloza, JP, Araya-Durán, I, Reyes, R, Vidaurre, S, Romero, V, Fuentes, J, Céric, F, Velásquez, L, González-Nilo, FD & Otero, C 2016, 'Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake' Nanoscale Research Letters, vol. 11, n.º 1, 66, pp. 1-13. DOI: 10.1186/s11671-016-1260-9

Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. / Márquez-Miranda, Valeria; Peñaloza, Juan Pablo; Araya-Durán, Ingrid; Reyes, Rodrigo; Vidaurre, Soledad; Romero, Valentina; Fuentes, Juan; Céric, Francisco; Velásquez, Luis; González-Nilo, Fernando D.; Otero, Carolina.

En: Nanoscale Research Letters, Vol. 11, N.º 1, 66, 01.12.2016, p. 1-13.

Resultado de la investigación: Contribución a la publicaciónArticle

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AU - Peñaloza,Juan Pablo

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AU - Reyes,Rodrigo

AU - Vidaurre,Soledad

AU - Romero,Valentina

AU - Fuentes,Juan

AU - Céric,Francisco

AU - Velásquez,Luis

AU - González-Nilo,Fernando D.

AU - Otero,Carolina

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Márquez-Miranda V, Peñaloza JP, Araya-Durán I, Reyes R, Vidaurre S, Romero V y otros. Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. Nanoscale Research Letters. 2016 dic 1;11(1):1-13. 66. Disponible desde, DOI: 10.1186/s11671-016-1260-9