Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery
Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery
复制标题
适体功能化 PEG-PLGA 纳米颗粒可增强抗神经胶质瘤药物输送
DOI：
10.1016/j.biomaterials.2011.07.004
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发表时间：
2011-11-01
期刊：
影响因子：
14
通讯作者：
Chen, Hongzhuan
中科院分区：
文献类型：
--
作者：
Guo, Jianwei;Gao, Xiaoling;Chen, Hongzhuan
以疾病特异性方式靶向递送治疗性纳米颗粒代表了一种潜在的强大技术，特别是在治疗浸润性脑肿瘤如神经胶质瘤时。我们开发了一种修饰有AS 1411（Ap）的纳米颗粒药物递送系统，AS 1411（Ap）是一种特异性结合核仁素的DNA适体，核仁素在癌细胞和血管生成血管中的内皮细胞的质膜中高度表达，作为靶向配体以促进紫杉醇（PTX）的抗胶质瘤递送。通过EDC/NHS技术将Ap缀合至PEG-PLGA纳米颗粒（NP）的表面。通过尿素PAGE和XPS确认缀合，所得Ap-PTX-NP为均匀圆形，粒度为156.0 +/-54.8nm，ζ电位为-32.93 +/-3.1mV。α p-核仁素相互作用显著增强了纳米颗粒在C6胶质瘤细胞中的细胞结合，并增加了其有效载荷的细胞毒性。Ap-FTX-NP实现了延长的循环和增强的PTX在肿瘤部位的积累，当与PTX-NP和Taxol（R）相比时，Ap-FTX-NP最终对携带C6神经胶质瘤异种移植物的小鼠获得了显著更高的肿瘤抑制，并延长了携带颅内C6神经胶质瘤的大鼠的动物存活。这一贡献的结果证明了AS 1411功能化纳米颗粒在神经胶质瘤治疗中的治疗应用的潜在效用。(C)2011爱思唯尔有限公司保留所有权利。
Targeted delivery of therapeutic nanoparticles in a disease-specific manner represents a potentially powerful technology especially when treating infiltrative brain tumors such as gliomas. We developed a nanoparticulate drug delivery system decorated with AS1411 (Ap), a DNA aptamer specifically binding to nucleolin which was highly expressed in the plasma membrane of both cancer cells and endothelial cells in angiogenic blood vessels, as the targeting ligand to facilitate anti-glioma delivery of paclitaxel (PTX). Ap was conjugated to the surface of PEG-PLGA nanoparticles (NP) via an EDC/NHS technique. With the conjugation confirmed by Urea PAGE and XPS, the resulting Ap-PTX-NP was uniformly round with particle size at 156.0 +/- 54.8 nm and zeta potential at -32.93 +/- 3.1 mV. Ap-nucleolin interaction significantly enhanced cellular association of nanoparticles in C6 glioma cells, and increased the cytotoxicity of its payload. Prolonged circulation and enhanced PTX accumulation at the tumor site was achieved for Ap-FTX-NP, which eventually obtained significantly higher tumor inhibition on mice bearing C6 glioma xenografts and prolonged animal survival on rats bearing intracranial C6 gliomas when compared with PTX-NP and Taxol (R). The results of this contribution demonstrated the potential utility of AS1411-functionalized nanoparticles for a therapeutic application in the treatment of gliomas. (C) 2011 Elsevier Ltd. All rights reserved.