Cerasome as an infusible, cell-friendly, and serum-compatible transfection agent in a viral size
Cerasome as an infusible, cell-friendly, and serum-compatible transfection agent in a viral size
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DOI：
10.1021/ja058016i
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发表时间：
2006-03-15
影响因子：
15
通讯作者：
Kikuchi, J
中科院分区：
文献类型：
--
作者：
Matsui, K;Sando, S;Kikuchi, J
季铵氮上具有 (EtO)3SiCH2CH2CH2 基团的丙氨酸阳离子脂质 1 形成脂质体，通过原位溶胶凝胶过程（Si−OEt + H2O → Si−OH + EtOH，然后 2Si−OH → Si−O−Si + H2O）在表面自硬化。所得的陶瓷体（部分陶瓷或二氧化硅包被的脂质体）（60−70 nm）在与荧光素酶编码质粒 DNA pGL3 的络合中保留了其完整性。所得的病毒大小（~70 nm）的不熔性或单体陶瓷体的 pGL3 复合物对 HeLa 和 HepG2 细胞表现出卓越的转染性能，效率高出 102-3 倍（相对于非甲硅烷基化参考脂质2）、最小化的细胞毒性和血清相容性。参考脂质2，即具有简单季铵化头基的基于丙氨酸的脂质，形成脂质体（60−70 nm），其自限制性较小且流动性更强，经过DNA诱导的融合，产生与内吞作用无关且毒性更大的更大（100−300 nm）颗粒。因此，硅策略提供了一种简单且广泛适用的工具来克服与当前人工基因递送技术相关的普遍问题。
Alanine-based cationic lipid1having a (EtO)3SiCH2CH2CH2group 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 lipid2), minimized cytotoxicity, and serum compatibility. Reference lipid2, 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.