The effect of functionalizing lipid nanocapsules with NFL-TBS.40-63 peptide on their uptake by glioblastoma cells

The effect of functionalizing lipid nanocapsules with NFL-TBS.40-63 peptide on their uptake by glioblastoma cells
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DOI:
10.1016/j.biomaterials.2013.01.068
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发表时间:
2013-04-01
期刊:
影响因子:
14
通讯作者:
Eyer, Joel
Eyer, Joel
中科院分区:
工程技术1区
文献类型:
--
作者:
Balzeau, Julien;Pinier, Maud;Eyer, Joel

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我们先前描述了一种神经丝衍生的细胞穿透肽NFL-TBS.40-63,其特异性地进入胶质母细胞瘤细胞,在那里它在体外和体内都干扰微管网络。本研究的目的是测试这种肽是否可以增加胶质母细胞瘤细胞对填充有Paclitaxel的脂质纳米胶囊的靶向摄取,从而可以增加其体外和体内的抗增殖作用。在这里,使用液滴张力测定法,我们表明大约60个NFL-TBS.40-63肽可以结合到一个50 nm的脂质纳米胶囊。当纳米胶囊填充有远红荧光染料(DiD)和Paclitaxel时,NFL-TBS.40-63肽的存在增加了它们被培养物中的胶质母细胞瘤细胞的摄取,如通过FACS分析所评估的,并因此降低了它们的增殖。最后,当将这种纳米胶囊注射到患有神经胶质瘤的小鼠中时,它们优先靶向肿瘤并减少其进展。这些结果表明,用NFL-TBS.40-63肽官能化的纳米帽代表了用于神经胶质瘤靶向治疗的强大的药物载体系统。(C)2013爱思唯尔有限公司保留所有权利。
We previously described a neurofilament derived cell-penetrating peptide, NFL-TBS.40-63, that specifically enters in glioblastoma cells where it disturbs the microtubule network both in vitro and in vivo. The aim of this study is to test whether this peptide can increase the targeted uptake by glioblastoma cells of lipid nanocapsules filled with Paclitaxel, and thus can increase their anti-proliferation in vitro and in vivo. Here, using the drop tensiometry we show that approximately 60 NFL-TBS.40-63 peptides can bind to one 50 nm lipid nanocapsule. When nanocapsules are filled with a far-red fluorochrome (DiD) and Paclitaxel, the presence of the NFL-TBS.40-63 peptide increases their uptake by glioblastoma cells in culture as evaluated by FACS analysis, and thus reduces their proliferation. Finally, when such nanocapsules were injected in mice bearing a glioma tumour, they are preferentially targeted to the tumour and reduce its progression. These results show that nanocapsules functionalized with the NFL-TBS.40-63 peptide represent a powerful drug-carrier system for glioma targeted treatment. (C) 2013 Elsevier Ltd. All rights reserved.