Design Principles of Lipid-like Ionic Liquids for Gene Delivery
David J. Siegel, Grace I. Anderson, Lauren M. Paul, Philipp J. Seibert, Patrick C. Hillesheim, Yinghong Sheng, Matthias Zeller, Andreas Taubert, P. Werner, Christian Balischewski, Scott F. Michael, Arsalan Mirjafari
Abstract
We developed lipid-like ionic liquids, containing 2-mercaptoimidazolium and 2-mercaptothiazolinium headgroups tethered to two long saturated alkyl chains, as carriers for in vitro delivery of plasmid HEK DNA into 293T cells. We employed a combination of modular design, synthesis, X-ray analysis, and computational modeling to rationalize the self-assembly and desired physicochemical and biological properties. The results suggest that thioamide-derived ionic liquids may serve as a modular platform for lipid-mediated gene delivery. This work represents a step toward understanding the structure-function relationships of these amphiphiles with long-range ordering and offering insight into design principles for synthetic vectors based on self-assembly behavior.