Cerasome as an Infusible, Cell-Friendly, and Serum-Compatible Transfection Agent in a Viral Size

Abstract

Alanine-based cationic lipid 1 having a (EtO)₃SiCH₂CH₂CH₂ group on the quaternized ammonium nitrogen forms a liposome which self-rigidifies via in situ sol−gel processes (Si−OEt + H₂O → Si−OH + EtOH followed by 2Si−OH → Si−O−Si + H₂O) on the surface. The resulting cerasome (partially ceramic- or silica-coated liposome) (60−70 nm) retains the integrity of such in the complexation with lucifarase-encoding plasmid DNA pGL3. The resultant pGL3 complex of infusible or monomeric cerasome in a viral size (∼70 nm) exhibits a remarkable transfection performance toward HeLa and HepG2 cells with a 10^2-3-fold higher efficiency (relative to that of the nonsilylated reference lipid 2), minimized cytotoxicity, and serum compatibility. Reference lipid 2, i.e., alanine-based lipid having a simple quaternized ammonium headgroup, forms liposome (60−70 nm) which is less self-confined and more mobile undergoes DNA-induced fusion to give endocytosis-irrelevant and more toxic bigger (100−300 nm) particles. The silicon strategy thus provides a simple and widely applicable tool to overcome general problems associated with current technology of artificial gene delivery.