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Sulfonium Lipids: Synthesis and Evaluation as DNA Delivery Vectors
Current Drug Delivery ( IF 2.8 ) Pub Date : 2022-05-22 , DOI: 10.2174/1567201819666220519122622
Jing Li 1 , Lei Zhang 1 , Yanjie Lu 1 , Yue Lin 1 , Kun Yang 1 , Xiaodong Zhou 1 , Guinan Shen 1
Affiliation  

Background: Cationic lipids can be used as nonviral vectors in gene delivery therapy. Most cationic lipids contain quaternary ammonium that can bond to negative phosphates of the plasmid. In this study, sulfonium—a trialkylated sulfur cation was adopted in the synthesis of a series of cationic lipids which were evaluated ability as gene delivery vectors. Methods: The sulfonium lipids were synthesized by condensing cyclic thioether and aliphatic carbon chains with ethoxy linkage and characterized the structure by NMR and mass. The DNA condensing abilities of sulfonium lipids were evaluated using a gel retardation experiment. Sulfonium lipids/DNA condensates were measured for particle size and Zeta potential. The cytotoxicity of sulfoniums was evaluated with MTT assay. The intracellular uptakes of sulfonium lipid/DNA complexes were observed with a fluorescence microscope. Results: The results showed that the sulfonium head can effectively bond to the phosphate of DNA. When S/P ratio is larger than 10/1, sulfonium lipids with longer carbon chains can completely condense DNA to form a nanoparticle with particle size ranging from 135 nm to 155 nm and zeta potential ranging from 28 mV to 42 mV. The IC50 of sulfonium lipids on HepG2 cells ranged from 2.37 μg/mL to 3.67 μg/mL. Cellular uptake experiments showed that sulfonium lipids/DNA condensate can be taken into cells Conclusion: Sulfonium lipids can effectively condense DNA and transfer DNA into cells. The sulfonium compound is worth of further development to reduce the cytotoxicity and increase transfection rate as gene vectors.

中文翻译:

硫脂质:作为 DNA 递送载体的合成和评估

背景:阳离子脂质可用作基因递送治疗中的非病毒载体。大多数阳离子脂质含有季铵盐,可以与质粒的负磷酸盐结合。在本研究中,硫鎓——一种三烷基化的硫阳离子被用于合成一系列阳离子脂质,评估其作为基因传递载体的能力。方法:硫脂质由环状硫醚和具有乙氧基键的脂肪族碳链缩合合成,并通过核磁共振和质谱对其结构进行表征。使用凝胶阻滞实验评估硫脂质的 DNA 凝聚能力。测量硫脂质/DNA 凝聚物的粒径和 Zeta 电位。MTT法测定硫鎓的细胞毒性。用荧光显微镜观察硫脂质/DNA 复合物的细胞内摄取。结果: 结果表明,硫头能有效地结合DNA的磷酸盐。当S/P比大于10/1时,具有较长碳链的硫脂质可以完全凝聚DNA,形成粒径为135 nm至155 nm、zeta电位为28 mV至42 mV的纳米粒子。硫脂质对 HepG2 细胞的 IC50 范围为 2.37 μg/mL 至 3.67 μg/mL。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。结果表明,硫头可以有效地结合DNA的磷酸盐。当S/P比大于10/1时,具有较长碳链的硫脂质可以完全凝聚DNA,形成粒径为135 nm至155 nm、zeta电位为28 mV至42 mV的纳米粒子。硫脂质对 HepG2 细胞的 IC50 范围为 2.37 μg/mL 至 3.67 μg/mL。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。结果表明,硫头可以有效地结合DNA的磷酸盐。当S/P比大于10/1时,具有较长碳链的硫脂质可以完全凝聚DNA,形成粒径为135 nm至155 nm、zeta电位为28 mV至42 mV的纳米粒子。硫脂质对 HepG2 细胞的 IC50 范围为 2.37 μg/mL 至 3.67 μg/mL。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。具有较长碳链的硫脂质可以完全凝聚 DNA 形成纳米颗粒,粒径范围为 135 nm 至 155 nm,zeta 电位范围为 28 mV 至 42 mV。硫脂质对 HepG2 细胞的 IC50 范围为 2.37 μg/mL 至 3.67 μg/mL。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。具有较长碳链的硫脂质可以完全凝聚 DNA 形成纳米颗粒,粒径范围为 135 nm 至 155 nm,zeta 电位范围为 28 mV 至 42 mV。硫脂质对 HepG2 细胞的 IC50 范围为 2.37 μg/mL 至 3.67 μg/mL。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。细胞摄取实验表明硫脂质/DNA 凝聚物可以被细胞摄取 结论:硫脂质可以有效地凝聚 DNA 并将 DNA 转移到细胞中。硫鎓化合物作为基因载体在降低细胞毒性和提高转染率方面值得进一步开发。
更新日期:2022-05-22
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