Journal
BIOCONJUGATE CHEMISTRY
Volume 24, Issue 9, Pages 1543-1551Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc400158w
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Funding
- Deutsche Forschungsgemeindchaft (DFG) as part of the Wnt Forschergruppe [FOR 1036]
- Helmholtz Association's Initiative and Networking Fund [VH-NG-621]
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Efficient delivery of plasmid DNA and siRNA into cells is essential for biological and biomedical research. Although significant efforts have been made to develop efficient nonviral vectors, such as cationic lipids and polymers, most of the vectors require multistep synthesis, which complicates both fast structural optimizations and combinatorial synthesis of such vectors. Here, we present a facile, single-step method based on an alkylation of amines, allowing for the fast parallel synthesis of libraries of cationic lipid-like molecules (lipidoids). We exploited the method to synthesize 200 lipidoids, which were screened for their transfection efficiency in HEK293T cells. The screen resulted in about 2% of new lipidoids capable of efficient cell transfection similar or higher than the efficiency of Lipofectamine 2000. In addition, we observed an enhancement of cellular transfection by combining single- with double-chain lipidoids, which was attributed to the different roles of the single- and double-tailed lipids in the mixed liposomes.
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