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首页> 外文期刊>Materials science & engineering >Arginine-tocopherol bioconjugated lipid vesicles for selective pTRAIL delivery and subsequent apoptosis induction in glioblastoma cells
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Arginine-tocopherol bioconjugated lipid vesicles for selective pTRAIL delivery and subsequent apoptosis induction in glioblastoma cells

机译：精氨酸 - 生育酚生物缀合的脂质囊泡，用于选择性Ptrail递送和胶质母细胞瘤细胞中随后的凋亡诱导

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摘要

The incorporation of specific therapeutic gene into glioblastoma offers potent therapeutic strategy to treat the disease. Non-viral gene delivery vectors are of particular interest due to their tuneable transfection efficiency and easy scale-up. Herein, we demonstrate successful delivery of plasmid encoding tumor necrosis factor (TNF)related apoptosis-inducing ligand (pTRAIL) using arginine-conjugated tocopherol lipid (AT) nanovesicles into glioblastoma cell lines. Another cationic lipid, glycine-conjugated tocopherol lipid (GT) having glycine in the head group region is also synthesized as a control lipid. Both lipid-derived liposomes effectively condensed the pDNA and the corresponding biomacromolecular assemblies (lipoplexes) are efficiently transfected into different cell lines. AT-based liposomes exhibit higher transfection efficacy in various cell lines, particularly selective in glioma cell lines. At an optimized N/P ratio, both the liposomal formulations show low cytotoxicity. AT-based lipoplexes have superior cellular uptake in U87 than the control lipid GT. The expression of TRAIL protein regulated death receptor and apoptosis signaling pathway is assayed by western blot using transfection of ATbased/pTRAIL into U87 cell lines. Induction of apoptosis in U87 cells exposed to AT-based/pTRAIL plasmid is evaluated by MTT assay as well as Annexin V-propidium iodide dual-staining assay. All results indicate that the developed AT-based/pTRAIL system offers a potentially safe and efficient therapeutic strategy for glioblastoma gene therapy.
机译：将特定治疗基因的掺入胶质母细胞瘤提供有效的治疗策略来治疗这种疾病。由于其可调谐转染效率和易扩展，非病毒基因递送载体特别感兴趣。在此，我们证明使用精氨酸缀合的生育酚脂质（AT）纳米粒子成胶质母细胞瘤细胞系来成功地递送质粒编码肿瘤坏死因子（TNF）相关的凋亡诱导的配体（PTRAIL）。另一个阳离子脂质，在头部区域中具有甘氨酸的甘氨酸缀合的生育酚脂质（GT）也被合成为对照脂质。脂质衍生的脂质体都有效地缩合了PDNA，并且相应的生物分子组件（脂质体）有效地转染到不同的细胞系中。基于基于脂质体在各种细胞系中表现出更高的转染功效，特别是在胶质瘤细胞系中选择性。在优化的N / P比下，脂质体配方均显示出低细胞毒性。在基于脂质上的脂质摄入优于对照脂质GT。通过将Atabased / Ptrail转染到U87细胞系中，通过Western印迹测定TRAIL蛋白调节死亡受体和凋亡信号通路的表达。通过MTT测定以及膜蛋白V-碘化丙酸碘化物双染料测定，评估暴露于基于/ Ptrail质粒的U87细胞中凋亡的诱导。所有结果表明，开发的基于/ Ptrail系统为胶质母细胞瘤基因疗法提供了潜在安全和有效的治疗策略。

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