Preparation, cellular uptake and angiogenic suppression of shikonin-containing liposomes in vitro and in vivo.
Preparation, cellular uptake and angiogenic suppression of shikonin-containing liposomes in vitro and in vivo.
复制标题
紫草素脂质体的体内外制备、细胞摄取及血管生成抑制
DOI：
10.1042/bsr20120065
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发表时间：
2013-02-01
影响因子：
4
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Xia H;Tang C;Gui H;Wang X;Qi J;Wang X;Yang Y
紫草素具有抗肿瘤活性，但尚未应用于临床。本文采用脂质体法制备紫草素。我们的目的是检查几个方面的sh-L（紫草素含脂质体）：制备，血管生成抑制和细胞摄取通过自身荧光。以大豆磷脂和胆固醇为原料制备Sh-L膜，将紫草素包封于磷脂膜中。以紫草素为原料制备了3种脂质体。它们具有红色荧光，并使用流式细胞仪进行分析。使用MTT [3-（4，5-二甲基噻唑-2-基）-2，5-二苯基-2H-溴化四唑]、Transwell试验、鸡CAM（绒毛尿囊膜）和Matrigel™塞测定来测定sh-L的血管生成抑制。MTT法测得紫草素、sh-L1和sh-L2的半数抑制浓度（IC_（50））分别为4.99±0.23、5.81±0.57和7.17±0.69 μM。3.15 μM紫草素、sh-L1和sh-L2的迁移抑制率分别为53.58±7.05，46.56±4.36和41.19±3.59%。CAM和Matrigel Plug实验结果表明紫草素和sh-L能减少新生血管的形成。在相同浓度下，紫草素的作用比sh-L更明显。结果表明，sh-L可降低细胞毒性，降低细胞迁移抑制率和血管生成抑制率。由于sh-L的自身荧光，可以描绘细胞摄取sh-L的情况。自荧光的产生将有助于进一步的研究。Sh-L可能是一个很好的制剂，为未来的临床应用于癌症患者。
Shikonin has anticancer activity, but it has not yet been applied into clinical use. In the present study, shikonin was prepared using liposomes. We aimed to examine several aspects of sh-L (shikonin-containing liposomes): preparation, angiogenic suppression and cellular uptake through self-fluorescence. Sh-L were prepared using soybean phospholipid and cholesterol to form the membrane and shikonin was encapsulated into the phospholipid membrane. Three liposomes were prepared with shikonin. They had red fluorescence and were analysed using a flow cytometer. Angiogenic suppression of sh-L was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide], Transwell tests, chick CAM (chorioallantoic membrane) and Matrigel™ plug assay. MTT assay showed the median IC50 (inhibitory concentrations) as follows: shikonin, sh-L1 and sh-L2 were 4.99±0.23, 5.81±0.57 and 7.17±0.69 μM, respectively. The inhibition rates of migration were 53.58±7.05, 46.56±4.36 and 41.19±3.59% for 3.15 μM shikonin, sh-L1 and sh-L2, respectively. The results of CAM and Matrigel plug assay demonstrated that shikonin and sh-L can decrease neovascularization. Effect of shikonin was more obvious than sh-L at the same concentration. The results showed that sh-L decreased the toxicity, the rate of inhibition of migration and angiogenic suppression. The cellular uptake of the sh-L could be pictured because of the self-fluorescence. The self-fluorescence will be useful for conducting further research. Sh-L might be an excellent preparation for future clinical application to cancer patients.