title: Quaternary ammonium groups exposed at the surface of silica nanoparticles suitable for DNA complexation in the presence of cationic lipids.
abstract: The production of silica nanoparticles (NPs) exposing quaternary ammonium groups (NPQ(+)) has been achieved using an optimized chemical surface functionalization protocol. The procedures of surface modification and quaternization of amino groups were validated by diffuse reflectance infrared Fourier transform (DRIFT) and (1)H NMR spectroscopies. Compared to nonquaternized aminated NP, the colloidal stability of NPQ(+) was improved for various pH and salt conditions as assessed by ζ potential and light scattering measurements. In the context of their use for nucleic acid delivery, DNA efficiently bound to NPQ(+) analyzed by cosedimentation assays for a large pH range and various NaCl concentrations and exhibited a better efficacy at basic pH than nonquaternized NP. The study of NPQ(+)/DNA/cationic lipids ternary complexes was carried out with 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and analyzed by cryo-electron microscopy (cryo-EM). Cryo-EM images showed ternary assemblies where condensed DNA strands are sandwiched between the NPQ(+) surface and the cationic lipid bilayer. Because of an unusual electrostatic colloidal stability of NPQ(+) and a high propensity to bind DNA molecules particularly at high salt concentrations, a novel type of ternary assembly has been formed that might impact the delivery properties of these complexes including their stability in biological environment.
authors.affiliation: †CNRS, ICMCB, UPR 9048, Université de Bordeaux, 87 avenue du Dr. A. Schweitzer, F-33600 Pessac, France.|‡CNRS, CRPP, UPR 8641, Université de Bordeaux, F-33600, Pessac, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Reinhardt
authors.affiliation: †CNRS, ICMCB, UPR 9048, Université de Bordeaux, 87 avenue du Dr. A. Schweitzer, F-33600 Pessac, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Adumeau
authors.affiliation: §CNRS, CBMN, UMR 5248, Université de Bordeaux, F-33402 Talence, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambert
authors.affiliation: ‡CNRS, CRPP, UPR 8641, Université de Bordeaux, F-33600, Pessac, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Ravaine
authors.affiliation: †CNRS, ICMCB, UPR 9048, Université de Bordeaux, 87 avenue du Dr. A. Schweitzer, F-33600 Pessac, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mornet
mesh_terms: D004247:DNA / Q000737:chemistry*; D005583:Fourier Analysis; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D008055:Lipids; D000644:Quaternary Ammonium Compounds; D012822:Silicon Dioxide; D004247:DNA