title: siRNA carriers based on carbosilane dendrimers affect zeta potential and size of phospholipid vesicles.
abstract: One of the major limitations in gene therapy is an inability of naked siRNA to passively diffuse through negatively charged cell membranes. Therefore, the siRNA transport into a cell requires efficient carriers. In this work we analyzed the charge-dependent interaction of the complexes of cationic carbosilane dendrimers (CBD) and anti-HIV siRNA (dendriplexes) with the model membranes - large unilamellar vesicles (LUV). We used the second generation of branched with CBD carbon-silicon bonds (CBD-CS) which are water-stable and that of oxygen-silicon bonds (CBD-OS) which are slowly hydrolyzed in aqueous solutions. The LUVs were composed of zwitterionic dimyristoylphosphatidylcholine (DMPC), negatively charged dipalmitoylphosphatidylglycerol (DPPG) and their mixture (DMPC/DPPG, molar ratio 7:3). The interaction of dendriplexes with LUVs affected both zeta potential and size of the vesicles. The changes of these values were larger for the negatively charged LUV. CBD-CS resulted in the decrease of zeta potential values to more negative ones, whereas an opposite effect took place for CBD-OS suggesting a different kind of interaction between LUVs and the dendriplexes. The results indicate that both CBD-CS and CBD-OS can be used for transport of siRNA into the cells. However, CBD-CS are preferred due to a better stability in water and improved bioavailability of siRNA on their surface.
authors.affiliation: Department of General Biophysics, University of Lodz, Lodz, Poland. maksion@biol.uni.lodz.pl
authors.forename: Maksim
authors.initials: M
authors.lastname: Ionov
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Garaiova
authors.forename: Iveta
authors.initials: I
authors.lastname: Waczulikova
authors.forename: Dominika
authors.initials: D
authors.lastname: Wróbel
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pędziwiatr-Werbicka
authors.forename: Rafael
authors.initials: R
authors.lastname: Gomez-Ramirez
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert
authors.forename: Tibor
authors.initials: T
authors.lastname: Hianik
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry; D001703:Biophysics / Q000379:methods; D002244:Carbon / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy / Q000379:methods; D006868:Hydrolysis; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism*; D012821:Silanes / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D050091:Dendrimers; D008055:Lipids; D008081:Liposomes; D010715:Phosphatidylglycerols; D010743:Phospholipids; D034741:RNA, Small Interfering; D012821:Silanes; C504072:carbosilane; D002244:Carbon; D010100:Oxygen; D004134:Dimyristoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol; D012825:Silicon