Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
复制标题
2-脱氧-D-葡萄糖功能化聚（乙二醇）-共聚（碳酸三亚甲基酯）纳米颗粒用于神经胶质瘤治疗中的双靶向药物递送
DOI：
10.1016/j.biomaterials.2013.09.094
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Fang, Xiaoling
中科院分区：
文献类型：
--
作者：
Jiang, Xinyi;Xin, Hongliang;Fang, Xiaoling
基于血脑屏障（BBB）和胶质瘤细胞上易化性葡萄糖转运蛋白（GLUT）的过表达，2-脱氧-D-葡萄糖修饰的聚乙二醇-聚三亚甲基碳酸酯纳米粒（DGlu-NP）被开发为潜在的双靶向药物递送系统，其通过GLUT介导的转胞吞作用增强血脑屏障的穿透和通过GLUT介导的内吞作用改善药物在胶质瘤中的蓄积。双靶向纳米粒系统的体外理化表征显示出令人满意的尺寸为71 nm，具有均匀分布、高包封率和足够的紫杉醇（PTX）负载量。与非葡萄糖基化纳米颗粒（NP）相比，RG-2胶质瘤细胞通过小窝介导和网格蛋白介导的内吞作用内化了显著更高量的DGlu-NP。DGlu-NP/PTX在体外血脑屏障模型中的转运率和RG-2细胞穿过血脑屏障后的细胞毒性均显著高于NP/PTX。体内荧光图像显示DGlu-NP对颅内肿瘤的聚集具有高度的特异性和效率。DGlu-NP/PTX的抗胶质母细胞瘤效果明显高于Taxol和NP/PTX。初步安全性试验显示，以100 mg/kg空白DGlu-NP/天的剂量静脉给药一周后，对小鼠血液系统、肝、肾、心、肺和脾均无急性毒性。因此，这些结果表明，DGlu-NP在本研究中开发的可能是一个潜在的双靶向治疗脑胶质瘤的车辆。(C)2013爱思唯尔有限公司保留所有权利。
Based on the facilitative glucose transporter (GLUT) over-expression on both blood-brain barrier (BBB) and glioma cells, 2-deoxy-D-glucose modified poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (DGlu-NP) were developed as a potential dual-targeted drug delivery system for enhancing the BBB penetration via GLUT-mediated transcytosis and improving the drug accumulation in the glioma via GLUT-mediated endocytosis. In vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of paclitaxel (PTX). Compared with non-glucosylated nanoparticles (NP), a significantly higher amount of DGlu-NP was internalized by RG-2 glioma cells through caveolae-mediated and clathrin-mediated endocytosis. Both of the transport ratios across the in vitro BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were significantly greater of DGlu-NP/PTX than that of NP/PTX. In vivo fluorescent image indicated that DGlu-NP had high specificity and efficiency in intracranial tumor accumulation. The anti-glioblastoma efficacy of DGlu-NP/PTX was significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary safety tests showed no acute toxicity to hematological system, liver, kidney, heart, lung and spleen in mice after intravenous administration at a dose of 100 mg/kg blank DGlu-NP per day for a week. Therefore, these results indicated that DGlu-NP developed in this study could be a potential dual-targeted vehicle for brain glioma therapy. (C) 2013 Elsevier Ltd. All rights reserved.