478. Preinjection of Free DiC14-Amidine Liposome and Dexamethasone Synergistically Enhance the Intravenous Transfection Efficiency of Cationic Lipid/DNA Lipoplex

Abstract

A new approach for generating cationic lipids for gene delivery bearing pyridinium polar heads was described recently 1. It is based on the reaction of pyrylium salts with primary amines thus generating the polar head and the linker of the non-viral transfection vector in a single, high yield step. The versatility of the synthesis allows the choice of a large variety of aliphatic or aromatic linkers, yielding cationic lipids such as 1–4, some of which act better than commercial transfection systems. The method also allows the easy access to the class of gemini surfactants such as 5 and congeners, and the facile choice of the counterion of the final positively charged species. Additionally, the use of styryl pyrylium salts can yield fluorescent transfection systems and membrane markers such as 6. Detailed insights into their chemical synthesis and transfection properties on different tumor cell lines are presented, together with a complete structure - activity relationship study for each class of lipophilic pyridinium compounds Figure 1.