Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction
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Fecha
2016-07
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Nature Publishing Group
Nombre de Curso
Licencia CC
Licencia CC
Resumen
An ideal nucleic-acid transfection system should combine the physical and chemical characteristics
of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous
research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on
polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of
lipids and preserve the high affinity for DNA possessed by cationic dendrimers. These lipid/dendrimer
hybrids consist of a low-generation, hydrophilic dendron (G2, G1, or G0) bonded to a hydrophobic
tail. The G2-18C AD was reported to be an efficient siRNA vector with significant gene silencing.
However, shorter tail ADs (G2-15C and G2-13C) and lower generation (G0 and G1) dendrimers failed as
transfection carriers. To date, the self-assembly phenomenon of this class of amphiphilic dendrimers
has not been molecularly explored using molecular simulation methods. To gain insight into these
systems, the present study used coarse-grained molecular dynamics simulations to describe how ADs
are able to self-assemble into an aggregate, and, specifically, how tail length and generation play a key
role in this event. Finally, explanations are given for the better efficiency of G2/18-C as gene carrier in
terms of binding of siRNA. This knowledge could be relevant for the design of novel, safer ADs with welloptimized
affinity for siRNA.
Notas
Indexación: Scopus
Palabras clave
Computational biology, Bioinformatics Computational, Biophysics
Citación
Scientific Reports Volume 6, 5 July 2016, Article number 29436