title: Time resolved SAXS to study the complexation of siRNA with cationic micelles of divalent surfactants.
abstract: The complexation of siRNA (small interfering RNA) with cationic micelles was studied using time dependent synchrotron SAXS. Micelles were formed by two types of divalent cationic surfactants, i.e. Gemini bis(quaternary ammonium) bromide with variable spacer length (12-3-12, 12-6-12, 12-12-12) and a weak electrolyte surfactant (SH14) with triazine head. Immediately after mixing (t < 50 ms), new large aggregates appeared in solution and the scattering intensity at low q increased. Concomitantly, the presence of a quasi-Bragg peak at q ∼ 1.5 nm(-1) indicated core structuring within the complexes. We hypothesize that siRNA and micelles are alternately arranged into "sandwiches", forming domains with internal structural coherence. The process of complex reorganization followed a first-order kinetics and was completed in less than about 5 minutes, after which a steady state was reached. Aggregates containing Geminis were compact globular structures whose gyration radii Rg depended on the spacer length and were in the order of 7-27 nm. Complexes containing SH14 (Rg = 14-16 nm) were less ordered and possessed a looser internal arrangement. The obtained data, joint with previous structural investigation using Dynamic Light Scattering, Zeta Potential and Small Angle Neutron Scattering, are encouraging evidence for using these systems in biological trials. In fact we showed that transfection agents can be obtained by simply mixing a micelle solution of the cationic surfactant and a siRNA solution, both of which are easily prepared and stable.
authors.affiliation: Department of Chemistry "Ugo Shiff" & CSGI, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, FI, Italy. ristori@unifi.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Falsini
authors.forename: Sandra
authors.initials: S
authors.lastname: Ristori
authors.forename: Laura
authors.initials: L
authors.lastname: Ciani
authors.forename: Emanuela
authors.initials: E
authors.lastname: Di Cola
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Annarosa
authors.initials: A
authors.lastname: Arcangeli
authors.forename: Martin
authors.initials: M
authors.lastname: In
mesh_terms: D002412:Cations / Q000737:chemistry; D007700:Kinetics; D008823:Micelles; D056004:Molecular Dynamics Simulation; D010316:Particle Size; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D053838:Scattering, Small Angle; D013501:Surface-Active Agents / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D002412:Cations; D008823:Micelles; D034741:RNA, Small Interfering; D013501:Surface-Active Agents