Kim Tae Woo, Kim Young Jin, Chung Hesson, Kwon Ick Chan, Sung Ha Chin, Jeong Seo Young
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hwawolkok-dong, Sungbuk-ku, Seoul, 136-791, South Korea.
J Control Release. 2002 Aug 21;82(2-3):455-65. doi: 10.1016/s0168-3659(02)00138-4.
Cationic lipid carriers were made of 1,2-dioleoyl-sn-glycero-3-trimethylammoniumpropane (DOTAP), squalene and different amounts of non-ionic surfactants. Various non-ionic surfactants were selected to elucidate the role of Tween 80 in the cationic lipid mediated gene delivery. They had a similar structure to Tween 80 such as various poly(ethyleneglycol) (PEG) chain lengths and acyl chain with different headgroups. For comparison, lipid carriers were also prepared with 1,2-dioleoyl-sn-glycero-3-trimethylammoniumpropane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Addition of non-ionic surfactants decreased the emulsion-DNA interaction and affected the transfection activity depending on the chain length and the content of PEG in the surfactant. Among the surfactants, Tween 80 yielded the best transgene expression without showing toxicity in COS-1 cells. The delivery mechanism of the complex was investigated by measuring the effects of endocytosis inhibitors (chloroquine and wortmannin). The emulsion-DNA complex seems to be taken up by the cells via endocytosis.
阳离子脂质载体由1,2 - 二油酰基 - sn - 甘油 - 3 - 三甲基铵丙烷（DOTAP）、角鲨烯和不同量的非离子表面活性剂制成。选择了各种非离子表面活性剂以阐明吐温80在阳离子脂质介导的基因递送中的作用。它们与吐温80具有相似的结构，例如具有不同头基的各种聚乙二醇（PEG）链长和酰基链。为了进行比较，还使用1,2 - 二油酰基 - sn - 甘油 - 3 - 三甲基铵丙烷（DOTAP）和1,2 - 二油酰基 - sn - 甘油 - 3 - 磷酸乙醇胺（DOPE）制备了脂质载体。添加非离子表面活性剂会降低乳液与DNA的相互作用，并根据表面活性剂中PEG的链长和含量影响转染活性。在这些表面活性剂中，吐温80在COS - 1细胞中产生了最佳的转基因表达且未显示出毒性。通过测量内吞作用抑制剂（氯喹和渥曼青霉素）的作用来研究复合物的递送机制。乳液 - DNA复合物似乎通过内吞作用被细胞摄取。
