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

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journal contribution
posted on 2006-03-15, 00:00 authored by Kazuki Matsui, Shinsuke Sando, Takashi Sera, Yasuhiro Aoyama, Yoshihiro Sasaki, Takayoshi Komatsu, Takashi Terashima, Jun-ichi Kikuchi
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 102-3-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.

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