Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells
Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells
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DOI：
10.1016/j.ijpharm.2016.07.066
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发表时间：
2016-09-25
影响因子：
5.8
通讯作者：
Santos, Helder A.
中科院分区：
文献类型：
--
作者：
Figueiredo, Patricia;Balasubramanian, Vimalkumar;Santos, Helder A.
基于聚二甲基硅氧烷-聚（2-甲基恶唑啉）（PDMS-PMOXA）二嵌段共聚物制成的聚合物囊泡（Ps），开发了一种针对多形性胶质母细胞瘤（GBM）的靶向药物递送纳米系统，以评估其主动靶向脑癌细胞并递送抗癌药物的潜力。将血管肽2偶联到预先形成的Ps的表面，以靶向在血脑屏障（BBB）和胶质瘤细胞中过表达的低密度脂蛋白受体相关蛋白I。血管肽2的缀合效率产率估计为24%。angiopep 2功能化的Ps在24小时后没有显示出细胞毒性，并且与非靶向Ps相比，在U87 MG胶质母细胞瘤细胞中增强了约5倍的细胞摄取。通过共溶剂法，阿霉素（DOX）在Ps中的包封率为13%，相比之下，薄膜再水化法（4%）。从Ps的DOX释放曲线显示在pH 5.5和pH 7.4下24小时后释放42%和40%，表明Ps可以有效地保留DOX，具有缓慢的释放速率。此外，与非靶向Ps相比，DOX负载的Ps-Angiopep 2的体外抗增殖活性显示出对U87 MG成胶质细胞瘤细胞的增强的毒性。总之，我们的体外结果表明，血管肽2缀合的Ps可用作纳米载体，用于向胶质母细胞瘤细胞有效靶向递送DOX。(C)© 2016 Elsevier B. V.版权所有。
A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor related protein I that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%. The angiopep2-functionalized Ps showed no cellular toxicity after 24 h and enhanced the cellular uptake around 5 times more in U87MG glioblastoma cells compared to the non-targeted Ps. The encapsulation efficiency of doxorubicin (DOX) in Ps was 13% by co-solvent method, compared to a film rehydration method (4%). The release profiles of the DOX from Ps showed a release of 42% at pH 5.5 and 40% at pH 7.4 after 24 h, indicating that Ps can efficiently retain the DOX with a slow release rate. Furthermore, the in vitro antiproliferative activity of DOX-loaded Ps-Angiopep2 showed enhanced toxicity to U87MG glioblastoma cells, compared to non -targeted Ps. Overall, our in vitro results suggested that angiopep2-conjugated Ps can be used as nanocarriers for efficient targeted DOX delivery to glioblastoma cells. (C) 2016 Elsevier B.V. All rights reserved.