Factors Determining the Superior Performance of Lipid/DNA/Protammine Nanoparticles over Lipoplexes
Factors Determining the Superior Performance of Lipid/DNA/Protammine Nanoparticles over Lipoplexes
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DOI：
10.1021/jm200237p
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发表时间：
2011-06-23
影响因子：
7.3
通讯作者：
Lagana, Aldo
中科院分区：
文献类型：
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作者：
Caracciolo, Giulio;Pozzi, Daniela;Lagana, Aldo
用蛋白蛋白/DNA复合物包被由阳离子1,2-二酰-3-三甲基丙烷铵（DOTAP）制成的脂质包膜，转染CHO（中国仓鼠卵巢细胞）、HEK293（人胚胎肾细胞）、NIH 3T3（小鼠胚胎细胞）和A17（小鼠癌细胞）细胞。采用广泛使用的DOTAP/DNA脂质体作为对照。在所有测试的细胞系中，脂质/鱼精蛋白/DNA （LPD）纳米颗粒在转染细胞时比脂质复合物更有效，尽管两种装置中脂质包膜的脂质组成相同。发现物理化学性质控制纳米载体在与细胞膜相互作用时释放DNA的能力。LPD复合物很容易释放它们的DNA载荷，而脂质体则基本保持完整并在细胞核中积累。总的来说，这些数据解释了为什么LPD纳米颗粒在转染细胞中通常表现出比脂质体更优越的性能，并代表了一种有前途的基因传递纳米载体。
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.