Kuznetsova Darya A, Kuznetsov Denis M, Vasileva Leysan A, Amerhanova Syumbelya K, Valeeva Dilyara N, Salakhieva Diana V, Nikolaeva Viktoriia A, Nizameev Irek R, Islamov Daut R, Usachev Konstantin S, Voloshina Alexandra D, Zakharova Lucia Ya
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, Russia.
Institute of Innovation Management, Kazan National Research Technological University, Karl Marx Str. 68, 420015 Kazan, Russia.
Pharmaceutics. 2022 Dec 1;14(12):2685. doi: 10.3390/pharmaceutics14122685.
Interaction between cationic surfactants and nucleic acids attracts much attention due to the possibility of using such systems for gene delivery. Herein, the lipoplexes based on cationic surfactants with imidazolium head group bearing methoxyphenyl fragment (MPI-n, n = 10, 12, 14, 16) and nucleic acids (oligonucleotide and plasmid DNA) were explored. The complex formation was confirmed by dynamic/electrophoretic light scattering, transmission electron microscopy, fluorescence spectroscopy, circular dichroism, and gel electrophoresis. The nanosized lipoplex formation (of about 100-200 nm), contributed by electrostatic, hydrophobic interactions, and intercalation mechanism, has been shown. Significant effects of the hydrocarbon tail length of surfactant and the type of nucleic acid on their interaction was revealed. The cytotoxic effect and transfection ability of lipoplexes studied were determined using M-HeLa, A549 cancer cell lines, and normal Chang liver cells. A selective reduced cytotoxic effect of the complexes on M-HeLa cancer cells was established, as well as a high ability of the systems to be transfected into cancer cells. MPI-n/DNA complexes showed a pronounced transfection activity equal to the commercial preparation Lipofectamine 3000. Thus, it has been shown that MPI-n surfactants are effective agents for nucleic acid condensation and can be considered as potential non-viral vectors for gene delivery.
阳离子表面活性剂与核酸之间的相互作用因有可能将此类体系用于基因递送而备受关注。在此，对基于带有甲氧基苯基片段的咪唑鎓头基阳离子表面活性剂（MPI-n，n = 10、12、14、16）与核酸（寡核苷酸和质粒DNA）的脂质体复合物进行了研究。通过动态/电泳光散射、透射电子显微镜、荧光光谱、圆二色性和凝胶电泳证实了复合物的形成。已表明通过静电、疏水相互作用和嵌入机制形成了纳米级脂质体复合物（约100 - 200 nm）。揭示了表面活性剂烃链长度和核酸类型对它们相互作用的显著影响。使用M-HeLa、A549癌细胞系和正常的Chang肝细胞测定了所研究脂质体复合物的细胞毒性作用和转染能力。确定了复合物对M-HeLa癌细胞的细胞毒性作用选择性降低，以及该体系向癌细胞转染的高能力。MPI-n/DNA复合物显示出与市售制剂Lipofectamine 3000相当的显著转染活性。因此，已表明MPI-n表面活性剂是核酸凝聚的有效试剂，可被视为潜在的非病毒基因递送载体。
