Imidazolium-Based Lipid Analogs as Lipofection Reagents

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Marco Pierau, Ronewa Nematswerani, Calvin Dunker, Frank Glorius, Anna Junker
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引用次数: 0

Abstract

Three imidazolium-based lipid analogs with varying degrees of saturation were synthesized and evaluated for their potential to enhance gene transfer in the 1321N1 and HEK-293FT cell lines. The analogs were incorporated into DPPC/DOPE-based liposomes and compared with two established transfection reagents, Lipofectamine3000 and FuGENE 4 K. Cytotoxicity assessments, as determined by lactate dehydrogenase assays, revealed a lower toxicity profile for the fully saturated compound 1 compared with its mono- (2) and di-unsaturated (3) counterparts. Notably, longer incubation times (24 h) amplified cytotoxic responses, with C17H31-IMeNMe3 (3) displaying the highest cell damage. Despite elevated toxicity relative to commercial reagents, compound 3 successfully delivered plasmid DNA using a PiggyBac transposon system, producing stable transfected cell lines after extended culture periods. C15H31-IMeNMe3 (1) achieved stable transfection but required longer colony expansion than the commercial controls, whereas C17H33-IMeNMe3 (2) did not yield transfected lines under the conditions tested. Overall, these results suggest that structural modifications, particularly the length of the alkyl chain and the number of double bonds, impact both cytotoxicity and transfection efficiency. The findings underscore the importance of rational lipid design, as stronger membrane interactions can enhance uptake while potentially heightening adverse effects. This study informs future development of safer, more effective nonviral delivery vectors.

Abstract Image

咪唑类脂质类似物作为吸脂试剂
合成了三种饱和度不同的咪唑类脂质类似物,并评估了它们在1321N1和HEK-293FT细胞系中促进基因转移的潜力。将类似物掺入DPPC/ dope基脂质体中,并与两种已建立的转染试剂Lipofectamine3000和FuGENE 4 K进行比较。通过乳酸脱氢酶测定的细胞毒性评估显示,与单不饱和化合物(2)和双不饱和化合物(3)相比,完全饱和化合物(1)的毒性更低。值得注意的是,较长的孵育时间(24小时)放大了细胞毒性反应,C17H31-IMeNMe3(3)显示出最大的细胞损伤。尽管与商业试剂相比毒性更高,但化合物 3利用PiggyBac转座子系统成功传递质粒DNA,在延长培养期后产生稳定的转染细胞系。C15H31-IMeNMe3(1)获得了稳定的转染,但比商业对照需要更长的菌落扩增时间,而C17H33-IMeNMe3(2)在测试条件下没有产生转染系。总的来说,这些结果表明结构修饰,特别是烷基链的长度和双键的数量,会影响细胞毒性和转染效率。这些发现强调了合理脂质设计的重要性,因为更强的膜相互作用可以增强摄取,同时潜在地增加不良反应。这项研究为未来开发更安全、更有效的非病毒传递载体提供了信息。
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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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