Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
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- 作者：Xinyi Jiang ; Hongliang Xin ; Qiuyue Ren ; Jijin Gu ; Lingjun Zhu ; Fengyi Du ; Chunlai Feng ; Yike Xie ; Xianyi Sha ; Xiaoling Fang
- 关键词：Glioma ; Dual-targeted drug delivery system ; Glucose transporter ; Endocytic mechanism ; Avascular glioma spheroids
- 刊名：Biomaterials
- 出版年：January, 2014
- 年：2014
- 卷：35
- 期：1
- 页码：518-529
- 全文大小：4120 K
文摘
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聽vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71聽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聽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聽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聽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.