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pH-sensitive N,N-(dimethyl)-N-alkanamine-N-oxides as gene delivery vectors

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Abstract

N,N-(Dimethyl)-N-alkanamine-N-oxides C n NO (n = 12 and 16) are amphiphiles that exist in neutral as well as in cationic forms depending on pH of aqueous solutions. C n NO with a neutral lipid DOPE (dioleoylphosphatidylethanolamine) can form liposomes with positive surface charge in acidic pH solution. C n NO/DOPE (n = 12 and 16) liposomes were used for preparation of DNA delivery vectors. Small-angle X-ray diffraction (SAXD) was used to determine the structure of C n NO/DOPE/DNA complexes prepared at various pH and 20 °C. At acidic pH, we observe a condensed lamellar phase LC with DNA strands packed regularly. With increasing pH, a coexistence of two lamellar phases is recognized. The amount of DNA bound into C n NO/DOPE/DNA complexes shows significant dependence on pH as derived from UV/Vis spectroscopy. Up to ~99% of total DNA was complexed at acidic pH. The cytotoxicity of C12NO/DOPE for HepG2 cells at acidic pH is low as determined by Janus Green Staining Assay.

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Acknowledgements

SAXD experiments were performed at BL11-NCD beamline at Alba Synchrotron with the collaboration of ALBA staff. The authors wish to thank Dr. Alexander Bucsi for his help at SAXD measurements. Experiments were supported by Grant VEGA 1/0916/16, grant FaF UK/22/2016, FaF UK/44/2016, HASYLAB project II-20100372 EC, JINR project 04-4-1121-2015/2017, APVV-0516-12 and APVV-0212-10. Part of the results utilizes knowledge gained from the project Center of excellence in security research (CEBV) ITMS 26240120034.

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  1. Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32, Bratislava, Slovakia

    Gilda Liskayová, Lukáš Hubčík, Dominika Galliková & Daniela Uhríková

  2. Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32, Bratislava, Slovakia

    Katarína Šišková & Ingrid Pauliková

  3. Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32, Bratislava, Slovakia

    Ferdinand Devínsky

  4. HASYLAB at DESY, Notkestr. 85, 22607, Hamburg, Germany

    Sergio S. Funari

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  1. Gilda Liskayová
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  2. Lukáš Hubčík
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Liskayová, G., Hubčík, L., Šišková, K. et al. pH-sensitive N,N-(dimethyl)-N-alkanamine-N-oxides as gene delivery vectors. Chem. Pap. 71, 1739–1748 (2017). https://doi.org/10.1007/s11696-017-0171-2

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