Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting
Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting
复制标题
大氨基酸转运蛋白1介导的谷氨酸修饰的负载多西他赛的脂质体用于神经胶质瘤靶向
DOI：
10.1016/j.colsurfb.2016.01.041
复制
发表时间：
2016-05-01
影响因子：
5.8
通讯作者：
He, Zhonggui
中科院分区：
文献类型：
--
作者：
Li, Lin;Di, Xingsheng;He, Zhonggui
血脑屏障（BBB）和胶质瘤的浸润性生长严重限制了胶质瘤的治疗效果。为解决这一难题，开发营养转运蛋白介导的双靶向给药系统，一方面用于血脑屏障穿透，另一方面用于脑胶质瘤靶向，受到越来越多的关注。在此，选择在BBB和胶质瘤细胞上过表达的大氨基酸转运蛋白1（LAT 1）作为靶标。应用装载多西他赛的谷氨酸-D-α-生育酚聚乙二醇1000琥珀酸酯共聚物（Glu-TPGS）功能化的LAT 1靶向脂质体（DTX-TGL）来增强BBB渗透和胶质瘤治疗。荧光图像的体内实验结果表明，TGL比未修饰的TGL具有更有效的小鼠血脑屏障穿透能力。在C6胶质瘤细胞中研究TGL对LAT 1的靶向性和细胞毒性。与未修饰的脂质体相比，TGL处理组的细胞摄取和细胞毒性显著增加。我们的研究结果表明，以LAT 1为靶点的紫杉醇脂质体为设计脑胶质瘤靶向纳米系统开辟了一个新的方向。(C)© 2016 Elsevier B. V.版权所有。
The therapeutic outcome of glioma treatment is rigorously limited by blood-brain barrier (BBB) and infiltrating growth of glioma. To tackle the dilemma, more and more attentions were focused on developing nutrient transporters-mediated dual-targeted drug delivery system, in one side for BBB penetration, another for intracranial glioma targeting. Herein, Large amino acid transporter 1 (LAT1), overexpressed both on BBB and glioma cells, was selected as a target. Docetaxel-loaded glutamate-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer (Glu-TPGS) functionalized LAT1-targeting liposomes (DTX-TGL) were applied to enhance the BBB penetration and glioma therapy. The in vivo results of the fluorescent image indicated that TGL possessed an effective BBB penetration than that of unmodified ones in mice. The LAT1 targeting effcicacy and cell cytotoxicity of TGL were investigated in C6 glioma cells. Compared with unmodified liposomes, a significant higher cellular uptake and cell cytotoxicity was found in TGL treated group. Our results indicated that LAT1-targeting docetaxel-loaded liposome paves up a new direction using LAT1 transporter as a good target in designing brain glioma-targeting nanosystems. (C) 2016 Elsevier B.V. All rights reserved.