Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration
Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration
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DOI：
10.1016/s1525-0016(03)00004-2
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发表时间：
2003-03-01
影响因子：
12.4
通讯作者：
Ramesh, R
中科院分区：
文献类型：
--
作者：
Ito, I;Began, G;Ramesh, R
我们已经研究了改进的脂质体制剂（挤出的DOTAP：胆固醇（DOTAP：Chol）-DNA复合物）在体外和体内对鼠和人来源的肿瘤细胞和正常细胞中的转基因表达的影响。在体外，与正常人细胞相比，人肿瘤细胞中的转基因表达显著增加（P = 0.01）。增加的转基因表达是由于肿瘤细胞吞噬作用增加了脂质体-DNA复合物的摄取。此外，免疫组化分析表明，肺肿瘤中的转基因表达比周围正常组织中的表达更高。使用荧光标记的DOTAP：Chol脂质体也证明了由于体内肿瘤细胞对脂质体-DNA复合物的摄取增强而增加的转基因表达。最后，对从接受肺切除术的患者中获得的肺组织外植体的评估表明，肿瘤细胞中的转基因表达显着高于（P = 0.001）正常细胞。因此，我们证明了静脉注射DOTAP：Chol-DNA复合物导致肿瘤中转基因表达增加，并且是由于肿瘤细胞对复合物的吞噬作用增加。
We have investigated the effects of an improved liposomal formulation (extruded DOTAP: cholesterol (DOTAP:Chol)-DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome-DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome-DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol-DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.