Protonation of Lipids Impacts the Supramolecular and Biological Properties of Their Self-Assembly

Autor: Marie Breton, Nathalie Mignet, Martin Hof, Daniel Scherman, Jean-François Berret, Michel Bessodes, Chantal Pichon, Teresa Kral, Claudie Bourgaux
Přispěvatelé: Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Rok vydání: 2011
Předmět:
MESH : DNA
01 natural sciences
chemistry.chemical_compound
Computational chemistry
MESH : Particle Size
Electrochemistry
Organic chemistry
MESH: Animals
General Materials Science
Spectroscopy
Liposome
Molecular Structure
Chemistry
Thiourea
MESH: DNA
Surfaces and Interfaces
Condensed Matter Physics
Lipids
MESH : Microscopy
Electron
Transmission
MESH: Microscopy
Electron
Transmission
lipids (amino acids
peptides
and proteins)
Protons
MESH: Cell Line
Tumor
Chemical structure
MESH: Molecular Structure
Supramolecular chemistry
Protonation
010402 general chemistry
MESH: Hydrodynamics
MESH: Thiourea
Microscopy
Electron
Transmission
Cell Line
Tumor
MESH : Hydrodynamics
Amphiphile
Animals
Humans
MESH : Protons
Molecule
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH : Thiourea
MESH: Particle Size
Particle Size
[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH: Humans
MESH : Cell Line
Tumor
010405 organic chemistry
MESH : Humans
MESH : Lipids
DNA
MESH: Lipids
0104 chemical sciences
Hydrodynamics
MESH: Protons
MESH : Animals
Self-assembly
MESH : Molecular Structure
Zdroj: Langmuir
Langmuir, American Chemical Society, 2011, 27 (20), pp.12336-45. 〈10.1021/la202439s〉
Langmuir, American Chemical Society, 2011, 27 (20), pp.12336-45. ⟨10.1021/la202439s⟩
ISSN: 1520-5827
0743-7463
DOI: 10.1021/la202439s
Popis: International audience; We assessed in this work how a chemical structure difference could influence a supramolecular organization and then its biological properties. In our case study, we considered two amphiphilic lipidic gene vectors. The chemical difference was situated on their hydrophilic part which was either a pure neutral thiourea head or a mixture of three thiourea function derivatives, thiourea, iminothiol, and charged iminothiol. This small difference was obtained thanks to the last chemical deprotection conditions of the polar head hydroxyl groups. Light, neutron, and X-ray scattering techniques have been used to investigate the spatial structure of the liposomes and lipoplexes formed by the lipids. The chemical structure difference impacts the supramolecular assemblies of the lipids and with DNA as shown by fluorescence correlation spectroscopy (FCS), X-ray, and neutron scattering. Hence the structures formed were found to be highly different in terms of liposomes to DNA ratio and size and polydispersity of the aggregates. Finally, the transfection and internalization results proved that the differences in the structure of the lipid aggregates fully affect the biological properties of the lipopolythiourea compounds. The lipid containing three functions is a better gene transfection agent than the lipid which only contains one thiourea moiety. As a conclusion, we showed that the conditions of the last chemical step can influence the lipidic supramolecular structure which in turn strongly impacts their biological properties.
Databáze: OpenAIRE
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