Folate-Equipped Pegylated Archaeal Lipid Derivatives: Synthesis and Transfection Properties

Graphical Abstract

DNA delivery: Tetra- and diether-type archaeal lipid analogues with a PEG chain and a folate moiety have been synthesised (see figure). These targeting co-lipids have afforded ligand–receptor internalisation of lipoplexes and efficient transfection of HeLa cells.

Abstract

We have previously shown that synthetic archaeal lipid analogues are useful vectors for drug/gene delivery. We report herein the synthesis and gene transfer properties of a series of novel di- and tetraether-type archaeal derivatives with a poly(ethylene glycol) (PEG) chain and further equipped with a folic acid (FA) group. The synthetic strategy and the purification by dialysis ensured complete removal of free FA. The lipids were mixed with a conventional glycine betaine-based cationic lipid and the resulting formulations were tested in transfection assays after complexation with plasmid DNA. All four novel co-lipids afforded efficient in vitro gene transfection. Moreover, the FA-equipped derivatives permitted ligand/receptor-based targeted transfection; their activity was inhibited when free FA was added to the transfection medium. These novel archaeal derivatives equipped with FA-PEG moieties may thus be of great interest for targeted in vivo transfection.