Precise glioblastoma targeting by AS1411 aptamer-functionalized poly (l-γ-glutamylglutamine)-paclitaxel nanoconjugates

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• 作者：Zimiao Luo^a ; Zhiqiang Yan^a ; Kai Jin^b ; Qiang Pang^b ; Ting Jiang^b ; Heng Lu^b ; Xianping Liu^b ; Zhiqing Pang^b ; ^{zqpang@fudan.edu.cn} ; Lei Yu^a ; ^{yulei@nbic.ecnu.edu.cn} ; Xinguo Jiang^b
• 关键词：Glioblastoma ; Aptamer ; Nucleolin ; Paclitaxel-nanoconjugate ; Targeting drug delivery system
• 刊名：Journal of Colloid and Interface Science
• 出版年：2017
• 出版时间：15 March 2017
• 年：2017
• 卷：490
• 期：Complete
• 页码：783-796
• 全文大小：5843 K
• 卷排序：490

文摘

Chemotherapy is still the main adjuvant strategy after surgery in glioblastoma therapy. As the main obstacles of chemotherapeutic drugs for glioblastoma treatment, the blood brain barrier (BBB) and non-specific delivery to non-tumor tissues greatly limit the accumulation of drugs into tumor tissues and simultaneously cause serious toxicity to nearby normal tissues which altogether compromised the chemotherapeutic effect. In the present study, we established an aptamer AS1411-functionalized poly (l-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX) nanoconjugates drug delivery system (AS1411-PGG-PTX), providing an advantageous solution of combining the precisely active targeting and the optimized solubilization of paclitaxel. The receptor nucleolin, highly expressed in glioblastoma U87 MG cells as well as neo-vascular endothelial cells, mediated the binding and endocytosis of AS1411-PGG-PTX nanoconjugates, leading to significantly enhanced uptake of AS1411-PGG-PTX nanoconjugates by tumor cells and three-dimension tumor spheroids, and intensive pro-apoptosis effect of AS1411-PGG-PTX nanoconjugates. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of AS1411-PGG-PTX as compared with PGG-PTX. As a result, the AS1411-PGG-PTX nanoconjugates presented the best anti-glioblastoma effect with prolonged median survival time and most tumor cell apoptosis in vivo as compared with other groups. In conclusion, the AS1411-PGG-PTX nanoconjugates exhibited a promising targeting delivery strategy for glioblastoma therapy.