TY - JOUR

T1 - Alkyl triphenylphosphonium surfactants as nucleic acid carriers

T2 - complexation efficacy toward DNA decamers, interaction with lipid bilayers and cytotoxicity studies

AU - Zakharova, Lucia Ya

AU - Kaupova, Guzalia I.

AU - Gabdrakhmanov, Dinar R.

AU - Gaynanova, Gulnara A.

AU - Ermakova, Elena A.

AU - Mukhitov, Alexander R.

AU - Galkina, Irina V.

AU - Cheresiz, Sergey V.

AU - Pokrovsky, Andrey G.

AU - Skvortsova, Polina V.

AU - Gogolev, Yuri V.

AU - Zuev, Yuriy F.

PY - 2019/8/14

Y1 - 2019/8/14

N2 - Herein, for the first time the complexation ability of a homological series of triphenylphosphonium surfactants (TPPB-n) toward DNA decamers has been explored. Formation of lipoplexes was confirmed by alternative techniques, including dynamic light scattering, indicating the occurrence of nanosized complexes (ca. 100-150 nm), and monitoring the charge neutralization of nucleotide phosphate groups and the fluorescence quenching of dye-intercalator ethidium bromide. The complexation efficacy of TPPB-surfactants toward an oligonucleotide (ONu) is compared with that of reference cationic surfactants. Strong effects of the alkyl chain length and the structure of the head group on the surfactant/ONu interaction are revealed, which probably occur via different mechanisms, with electrostatic and hydrophobic forces or intercalation imbedding involved. Phosphonium surfactants are shown to be capable of disordering lipid bilayers, which is supported by a decrease in the temperature of the main phase transition, Tm. This effect enhances with an increase in the alkyl chain length, indicating the integration of TPPB-n with lipid membranes. This markedly differs from the behavior of typical cationic surfactant cetyltrimethylammonium bromide, which induces an increase in the Tm value. It was demonstrated that the cytotoxicity of TPPB-n in terms of the MTT-test on a human cell line 293T nonmonotonically changes within the homological series, with the highest cytotoxicity exhibited by the dodecyl and tetradecyl homologs.

AB - Herein, for the first time the complexation ability of a homological series of triphenylphosphonium surfactants (TPPB-n) toward DNA decamers has been explored. Formation of lipoplexes was confirmed by alternative techniques, including dynamic light scattering, indicating the occurrence of nanosized complexes (ca. 100-150 nm), and monitoring the charge neutralization of nucleotide phosphate groups and the fluorescence quenching of dye-intercalator ethidium bromide. The complexation efficacy of TPPB-surfactants toward an oligonucleotide (ONu) is compared with that of reference cationic surfactants. Strong effects of the alkyl chain length and the structure of the head group on the surfactant/ONu interaction are revealed, which probably occur via different mechanisms, with electrostatic and hydrophobic forces or intercalation imbedding involved. Phosphonium surfactants are shown to be capable of disordering lipid bilayers, which is supported by a decrease in the temperature of the main phase transition, Tm. This effect enhances with an increase in the alkyl chain length, indicating the integration of TPPB-n with lipid membranes. This markedly differs from the behavior of typical cationic surfactant cetyltrimethylammonium bromide, which induces an increase in the Tm value. It was demonstrated that the cytotoxicity of TPPB-n in terms of the MTT-test on a human cell line 293T nonmonotonically changes within the homological series, with the highest cytotoxicity exhibited by the dodecyl and tetradecyl homologs.

UR - http://www.scopus.com/inward/record.url?scp=85070789644&partnerID=8YFLogxK

U2 - 10.1039/c9cp02384d

DO - 10.1039/c9cp02384d

M3 - Article

C2 - 31321392

AN - SCOPUS:85070789644

VL - 21

SP - 16706

EP - 16717

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 30

ER -