DOPE facilitates quaternized lipidoids (QLDs) for in vitro DNA delivery

This paper describes the synthesis of a combinatorial library of quaternized lipidoids (QLDs) and an evaluation of their abilities to facilitate in vitro DNA delivery. The QLDs alone showed low efficiency for DNA delivery. By formulating liposomes with a neutral helper lipid, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), the capability of QLDs for gene transfection is significantly enhanced due to the fusogenic properties of DOPE which facilitate endosomal escape and cargo delivery. We further optimized the liposome composition and DNA dose for gene transfection and investigated the structure–activity relationships of the lipidoid library in DNA delivery.From the Clinical EditorThis paper describes the synthesis and evaluation of a combinatorial library of quaternized lipidoids to facilitate in vitro DNA delivery, which occurs at a low level but can be enhanced with DOPE. The authors also further optimized the liposome composition and DNA dose for delivery and investigated the structure-activity relationships of the lipidoid library.

Graphical AbstractA combinatorial library of lipid-like materials termed “lipidoids” is attractive as a new class of non-viral delivery vectors due to their easy and economic combinatorial synthesis, as well as their high delivery efficiencies. However, the quaternized lipidoids (QLDs) alone showed low efficiency for DNA delivery. By formulating liposomes with a neutral helper lipid, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), we demonstrated the capability of QLDs for gene transfection is significantly enhanced, with an efficiency even higher than the commercial transfection agent, Lipofectamine 2000. These materials and formulations are also useful for delivery of other nucleic acid-based cargos.Figure optionsDownload high-quality image (75 K)Download as PowerPoint slide