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Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake
Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH(2)) 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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742457/ https://www.ncbi.nlm.nih.gov/pubmed/26847692 http://dx.doi.org/10.1186/s11671-016-1260-9 |
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author | 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 |
author_facet | 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 |
author_sort | Márquez-Miranda, Valeria |
collection | PubMed |
description | Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH(2)) 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-NH(2) 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-NH(2), 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-NH(2) 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. |
format | Online Article Text |
id | pubmed-4742457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-47424572016-02-16 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 Nanoscale Res Lett Nano Express Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH(2)) 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-NH(2) 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-NH(2), 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-NH(2) 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. Springer US 2016-02-04 /pmc/articles/PMC4742457/ /pubmed/26847692 http://dx.doi.org/10.1186/s11671-016-1260-9 Text en © Márquez-Miranda et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Nano Express 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 |
title | Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake |
title_full | Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake |
title_fullStr | Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake |
title_full_unstemmed | Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake |
title_short | Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake |
title_sort | effect of terminal groups of dendrimers in the complexation with antisense oligonucleotides and cell uptake |
topic | Nano Express |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742457/ https://www.ncbi.nlm.nih.gov/pubmed/26847692 http://dx.doi.org/10.1186/s11671-016-1260-9 |
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