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

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dc.contributor.authorMárquez Miranda, Valeria
dc.contributor.authorPeñaloza, Juan Pablo
dc.contributor.authorAraya Duran, Ingrid
dc.contributor.authorReyes, Rodrigo
dc.contributor.authorVidaurre, Soledad
dc.contributor.authorRomero, Valentina
dc.contributor.authorFuentes, Juan
dc.contributor.authorCeric, Francisco
dc.contributor.authorVelásquez, Luis
dc.contributor.authorGonzález Nilo, Fernando
dc.date.accessioned2016-10-28T19:58:25Z
dc.date.available2016-10-28T19:58:25Z
dc.date.issued2016
dc.description.abstractPoly (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.
dc.identifier.citationMárquez-Miranda V, Peñaloza JP, Araya-Durán I, Reyes R, Vidaurre S, Romero V, Fuentes J, Céric F, Velásquez L, González-Nilo FD, Otero C. Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. Nanoscale Res Lett. 2016 Dec;11(1):66.
dc.identifier.urihttp://hdl.handle.net/11447/808
dc.identifier.urihttp://dx.doi.org/10.1186/s11671-016-1260-9
dc.language.isoen_US
dc.subjectPamam Dendrimers
dc.subjectPolymidoamine Dendrimers
dc.subjectMolecular-Dynamics
dc.subjectGene Delivery
dc.subjectRas-Raf
dc.subjectSurface
dc.subjectCáncer
dc.subjectTransfection
dc.subjectEndocytosis
dc.subjectENDOCYTOSIS
dc.subjectTrafficking
dc.titleEffect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake
dc.typeArtículo

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