Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK.
Pharm Res. 2009 Oct;26(10):2237-46. doi: 10.1007/s11095-009-9940-0. Epub 2009 Jul 22.
To investigate the arsonoliposome effect on medulloblastoma cells (VC312Rs) related to uptake, endocytotic mechanism and cell viability.
VC312R viability in presence of either arsonoliposomes or stealth liposomes was studied using MTT assay for 1-4 days. Fibroblasts (3T3) were used as control. Apoptosis was studied for 2 h, 5 h and 24 h. Bodipy-labelled arsonoliposome uptake (time- and dose-dependent) was estimated using FACS analysis. The endocytotic mechanism was investigated using inhibitors of clathrin- (chlorpromazine) and caveolae-mediated endocytosis (filipin).
Arsonoliposomes affected significantly the VC312R viability compared to 3T3 cells and induced apoptosis to VC312Rs after 2 h of incubation. Apoptosis was not observed for 3T3 cells. Liposome uptake versus time showed a bimodal pattern. Clathrin-mediated endocytosis was the main endocytotic mechanism at low lipid concentrations and caveolae at higher ones; thus, dose-dependent uptake did not show a plateau at increased lipid concentrations.
Arsonoliposomes showed "selective" toxicity towards medulloblastoma cells inducing apoptosis after 2 hs of incubation. Therefore, arsonoliposomes are promising anticancer vehicles for brain tumour treatment.
研究纵火脂质体对神经母细胞瘤细胞（VC312Rs）摄取、内吞机制和细胞活力的影响。
用 MTT 法在存在纵火脂质体或隐形脂质体的情况下研究 VC312R 活力，持续 1-4 天。用成纤维细胞（3T3）作为对照。研究凋亡 2 小时、5 小时和 24 小时。用流式细胞术分析估计 BODIPY 标记的纵火脂质体摄取（时间和剂量依赖性）。用网格蛋白和 caveolae 介导的内吞抑制剂研究内吞机制。
与 3T3 细胞相比，纵火脂质体显著影响 VC312R 的活力，并在孵育 2 小时后诱导 VC312R 凋亡。3T3 细胞未观察到凋亡。脂质体摄取与时间呈双峰模式。在低脂质浓度下，网格蛋白介导的内吞是主要的内吞机制，而在较高浓度下则是 caveolae；因此，在增加脂质浓度时，剂量依赖性摄取不会出现平台。
纵火脂质体对神经母细胞瘤细胞具有“选择性”毒性，在孵育 2 小时后诱导凋亡。因此，纵火脂质体是治疗脑肿瘤的有前途的抗癌载体。
