Cerasome as an infusible, cell-friendly, and serum-compatible transfection agent in a viral size |
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Authors: | Matsui Kazuki Sando Shinsuke Sera Takashi Aoyama Yasuhiro Sasaki Yoshihiro Komatsu Takayoshi Terashima Takashi Kikuchi Jun-ichi |
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Institution: | Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan. |
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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 ( approximately 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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