Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6112, USA.
Mol Pharm. 2010 Jun 7;7(3):786-94. doi: 10.1021/mp900298f.
We, and others, have observed that the structure of cationic lipids appears to have a significant effect on the transfection efficacy of optimized nucleic acid/cationic lipid complexes (lipoplexes) used for in vitro and in vivo gene delivery and expression. Although there are many in vitro comparisons of lipid reagents for gene delivery, few comparisons have been made in vivo. We previously reported the effects of changes in hydrophobic domain chain length and chain asymmetry, changes in headgroup composition, and counterion exchange. We have observed in our own work over many years the apparent superiority of asymmetric versus symmetric hydrocarbon domains for otherwise similar lipids. In this investigation we use in vivo whole animal brain imaging to evaluate the contribution of symmetric versus asymmetric hydrophobic domains on what we previously determined to be optimal chain lengths for in vitro transfections. We specifically investigated several glycerol-based lipids; however, the rare reports of asymmetric non-glycerol-based lipids also support our observations. We found that asymmetric, two-chain cationic lipids of 14 to 18 carbons perform significantly better in vivo, as analyzed by whole animal imaging, than the paired symmetric lipids.
我们和其他人观察到，阳离子脂质的结构似乎对用于体外和体内基因传递和表达的优化核酸/阳离子脂质复合物（脂质体）的转染效率有重大影响。尽管有许多关于用于基因传递的脂质试剂的体外比较，但在体内进行的比较很少。我们之前报道了改变疏水区链长和链不对称性、改变头基组成和反离子交换的影响。在多年的工作中，我们观察到对于其他方面相似的脂质，不对称烃域优于对称烃域。在这项研究中，我们使用体内全动物脑成像来评估对称与不对称疏水区对我们之前确定的体外转染最佳链长的贡献。我们专门研究了几种基于甘油的脂质；然而，关于不对称非甘油基脂质的罕见报道也支持我们的观察结果。我们发现，通过全动物成像分析，具有 14 到 18 个碳原子的不对称、双链阳离子脂质在体内的性能明显优于配对的对称脂质。
