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三取代锍类化合物的合成及其基因载体能力研究

Synthesis of Trisubstituted Sulfonium Compounds and Study of Their Gene Carrier Abilities
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摘要 阳离子脂质作为基因载体被广泛研究。以锍离子为阳离子头构建阳离子脂质,开发其基因载体的能力。通过有机合成方法合成了4个锍化合物,应用质谱、核磁对其表征;通过凝胶电泳阻滞实验评价化合物对DNA的复合能力,选择能够完全复合DNA的2个化合物,利用动态光散射实验测试其复合物的粒径和Zeta电势,通过透射电镜观察复合物形态学特征,通过MTT实验测试2个化合物对细胞存活率的影响,最后通过激光共聚焦显微镜观察复合物粒子的细胞内吞效果。结果发现:锍化合物的烷烃链增长时,对DNA的复合能力增强,复合物呈球状,纳米粒径在200~400 nm,Zeta电势为正。该组锍类化合物在HepG 2细胞上IC50值在0.40~0.45 nmol·mL^(-1)之间,细胞对复合物有一定的内吞能力,但效率略低。表明应用锍离子头构建阳离子脂质基因载体可行,所连接的基团还需要深入探索。 Cationic lipids have been widely studied as gene carriers.Sulfonium as cationic headgroup is potent to form cationic lipids as gene carriers.Four sulfonium compounds were synthesized by organic synthesis and characterized by mass spectrometry and NMR.The DNA recombination ability of the compounds was evaluated by gel electrophoresis retardation experiment.Two compounds that could completely recombine DNA were selected,the particle size and Zeta potential of the compounds were tested by dynamic light scattering experiment,the morphological characteristics of the compounds were observed by transmission electron microscopy,and the effects of the two compounds on the cell survival rate were tested by MTT experiment.Finally,the endocytosis effect of the complex particles was observed by laser confocal microscopy.It was found that when the alkane chain of sulfonium compound increased,the DNA recombination ability was enhanced,the complex was spherical,the particle size was 200-400 nm,and the Zeta potential was positive.The IC50 values of these sulfonium compounds on HepG-2 cells ranged from 0.40 to 0.45 nmol·mL^(-1),and the cells had a certain endocytosis capacity for the complex,but the efficiency was slightly lower.The results showed that it was feasible to construct cationic lipid gene carriers using sulfonium ion heads,but the linked groups would need to be further explored.
作者 柳丙玲 张雷 刘成才 陈玥 李婧 Liu Bingling;Zhang Lei;Liu Chengcai;Chen Yue;Li Jing(College of Life Science and Biotechnology,Heilongjiang Bayi Agricultural University,Daqing 163319;Testing Center,Heilongjiang Bayi Agriculture University;Mudanjiang Institute for Food and Biotechnology Innovation,Heilongjiang Bayi Agriculture University)
出处 《黑龙江八一农垦大学学报》 2024年第6期86-92,共7页 journal of heilongjiang bayi agricultural university
基金 黑龙江省自然科学基金(SS2022B001) 黑龙江省博士后科研启动资助项目(LBH-Q15115) 黑龙江省“双一流”二期建设学科协同创新特区建设项目(LJGXCG2022-006) 黑龙江八一农垦大学三横三纵基金(ZRCPY202112)。
关键词 基因递送 阳离子脂质 锍类化合物 DNA复合物 gene delivery cationic lipid sulfonium compound DNA complex
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