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.
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.