title: Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction.
abstract: 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 well-optimized affinity for siRNA.
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Av. República 239, Santiago, Chile.|Fundación Fraunhofer Chile Research, Las Condes, Chile.
authors.forename: Valeria
authors.initials: V
authors.lastname: Márquez-Miranda
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Av. República 239, Santiago, Chile.|Fundación Fraunhofer Chile Research, Las Condes, Chile.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Araya-Durán
authors.affiliation: Universidad Bernardo O Higgins, Laboratorio de Bionanotecnología, General Gana 1702, Santiago, Chile.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Camarada
authors.affiliation: Kansas State University, Nanotechnology Innovation Center of Kansas State, Institute of Computational Comparative Medicine, Anatomy and Physiology, Kansas, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Comer
authors.affiliation: Centro de Biotecnología FEMSA, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Col. Tecnológico, Monterrey, N.L, México.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Valencia-Gallegos
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Av. República 239, Santiago, Chile.|Fundación Fraunhofer Chile Research, Las Condes, Chile.|Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Fernando Danilo
authors.initials: FD
authors.lastname: González-Nilo
mesh_terms: D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
chemical_list: D050091:Dendrimers; D008055:Lipids; D034741:RNA, Small Interfering