Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.
J Med Chem. 2011 Jun 23;54(12):4160-71. doi: 10.1021/jm200237p. Epub 2011 May 26.
The utility of using a protammine/DNA complex coated with a lipid envelope made of cationic 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) for transfecting CHO (Chinese hamster ovary cells), HEK293 (human embryonic kidney cells), NIH 3T3 (mouse embryonal cells), and A17 (murine cancer cells) cells was examined. The widely used DOTAP/DNA lipoplex was employed as a reference. In all the tested cell lines lipid/protamine/DNA (LPD) nanoparticles were more efficient in transfecting cells than lipoplexes even though the lipid composition of the lipid envelope was the same in both devices. Physical-chemical properties were found to control the ability of nanocarriers to release DNA upon interaction with cellular membranes. LPD complexes easily release their DNA payload, while lipoplexes remain largely intact and accumulate at the cell nucleus. Collectively, these data explain why LPD nanoparticles often exhibit superior performances compared to lipoplexes in trasfecting cells and represent a promising class of nanocarriers for gene delivery.
研究了一种带有正电 1,2-二油酰基-3-三甲基铵丙烷 (DOTAP) 脂质包膜的鱼精蛋白/DNA 复合物用于转染 CHO（中国仓鼠卵巢细胞）、HEK293（人胚肾细胞）、NIH 3T3（小鼠胚胎细胞）和 A17（鼠癌细胞）细胞的效用。广泛使用的 DOTAP/DNA 脂质体被用作参考。在所有测试的细胞系中，即使脂质包膜的脂质组成在两种装置中相同，脂质/鱼精蛋白/DNA（LPD）纳米颗粒在转染细胞方面也比脂质体更有效。研究发现，物理化学性质控制着纳米载体与细胞膜相互作用时释放 DNA 的能力。LPD 复合物很容易释放其 DNA 有效载荷，而脂质体则基本保持完整并聚集在细胞核中。总的来说，这些数据解释了为什么 LPD 纳米颗粒在转染细胞方面通常比脂质体表现出更好的性能，并代表了一类用于基因传递的有前途的纳米载体。
