pH-Sensitive N,N-Dimethylalkane-1-amine N-Oxides in DNA Delivery: From Structure to Transfection Efficiency
| Autor: | Lukáš Hubčík, Alexander Búcsi, Mária Hanulová, Juan Carlos Martínez, Daniela Uhríková, Sandra Ritz, Tomas Fazekas, Ferdinand Devínsky, Gilda Liskayová, Martin Pisárčik |
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| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
Liposome Small-angle X-ray scattering Chemistry Substituent 02 engineering and technology Surfaces and Interfaces Transfection 010402 general chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics 01 natural sciences 0104 chemical sciences Crystallography chemistry.chemical_compound Lipofectamine Electrochemistry Zeta potential lipids (amino acids peptides and proteins) General Materials Science Lamellar structure 0210 nano-technology Spectroscopy Alkyl |
| Zdroj: | Langmuir. 35:13382-13395 |
| ISSN: | 1520-5827 0743-7463 |
| DOI: | 10.1021/acs.langmuir.9b02353 |
| Popis: | pH-sensitive liposomes composed of homologues of series of N,N-dimethylalkane-1-amine N-oxides (CnNO, n = 8-18, where n is the number of carbon atoms in the alkyl substituent) and neutral phospholipid dioleoylphosphatidylethanolamine (DOPE) were prepared at two molar ratios (CnNO/DOPE = 0.4:1 and 1:1) and tested for their in vitro transfection activity. Several techniques (SAXS/WAXS, UV-vis, zeta potential measurements, confocal microscopy) were applied to characterize the system in an effort to unravel the relationship among the transfection efficiency, structure, and composition of the lipoplexes. The transfection efficiency of CnNO/DOPE for plasmid DNA in U2OS cells follows a quasi-parabolic dependence on CnNO's alkyl substituent length with a maximum at n = 16. The transfection efficiency of CnNO/DOPE (n = 12-18) lipoplexes was found to be higher than that of commercially available Lipofectamine 2000. C16NO/DOPE also positively transfected HEK 293T and HeLa cells. Small-angle X-ray scattering (SAXS) shows large structural diversity depending on the complex's composition and pH. Transfection efficiencies mediated by two structures, either a condensed lamellar (Lαc) or epitaxially connected Lαc and a condensed inverted hexagonal (HIIc) phase (Lαc & HIIc), were found to be very similar. The change in pH from acidic to neutral induces phase transition Lαc & HIIc → QII + Lα, with cubic phase QII of the Pn3m space group. QII detected in lipoplexes of most efficient composition CnNO/DOPE (n = 16 and 18) facilitates DNA release and promotes its internalization in the cell. |
| Databáze: | OpenAIRE |
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