title: Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake.
abstract: 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.
authors: Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Universidad Andres Bello, Republica 239, Santiago, Chile.|Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile.
authors: Valeria
authors: V
authors: Márquez-Miranda
authors: Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.
authors: Juan Pablo
authors: JP
authors: Peñaloza
authors: Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Universidad Andres Bello, Republica 239, Santiago, Chile.|Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile.
authors: Ingrid
authors: I
authors: Araya-Durán
authors: Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.
authors: Rodrigo
authors: R
authors: Reyes
authors: Departamento Ciencias Químicas y Biológicas, Laboratorio de Bionanotecnología, Universidad Bernardo O'Higgins, Santiago, Chile.
authors: Soledad
authors: S
authors: Vidaurre
authors: Departamento Ciencias Químicas y Biológicas, Laboratorio de Bionanotecnología, Universidad Bernardo O'Higgins, Santiago, Chile.
authors: Valentina
authors: V
authors: Romero
authors: Facultad de Biología, Laboratorio de Microbiología, Universidad Andres Bello, Republica 217, Santiago, Chile.
authors: Juan
authors: J
authors: Fuentes
authors: Laboratorio de Neurociencias Cognitivas, Facultad de Psicología, Universidad del Desarrollo, Santiago, Chile.
authors: Francisco
authors: F
authors: Céric
authors: Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile.|Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.
authors: Luis
authors: L
authors: Velásquez
authors: Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Universidad Andres Bello, Republica 239, Santiago, Chile. fernando.gonzalez@unab.cl.|Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile. fernando.gonzalez@unab.cl.|Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile. fernando.gonzalez@unab.cl.
authors: Fernando D
authors: FD
authors: González-Nilo
authors: Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes, Chile. maria.otero@unab.cl.|Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile. maria.otero@unab.cl.
authors: Carolina
authors: C
authors: Otero