Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1
Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1
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DOI：
10.3109/10717544.2013.876460
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发表时间：
2015-05-01
期刊：
影响因子：
6
通讯作者：
Chekhonin, Vladimir P.
中科院分区：
文献类型：
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作者：
Baklaushev, Vladimir P.;Nukolova, Natalia N.;Chekhonin, Vladimir P.
脑肿瘤的靶向给药是纳米医学的重要目标之一。人脑胶质母细胞瘤是最常见和侵袭性最强的脑肿瘤。膜蛋白连接蛋白43(Cx43)和脑特异性阴离子转运体(BSAT1)在肿瘤及瘤周区域的优先表达是靶向给药的关键组成部分。本研究的目的是设计与抗Cx43和BSAT1单抗结合的顺铂纳米凝胶治疗脑胶质瘤101/8。对荷瘤大鼠的MRI体积分析表明，与其他剂型相比，顺铂靶向纳米凝胶治疗显著缩小了肿瘤体积。抗Cx43和BSAT1胞外环的靶向纳米凝胶治疗组大鼠的中位生存期分别比对照组高27天和26.6天。我们首次在胶质瘤101/8实验模型中证实了单抗靶向顺铂纳米凝胶的有效性。这种方法可以促进新的药物释放系统的开发，用于治疗胶质瘤。
Targeted drug delivery for brain tumor treatment is one of the important objectives in nanomedicine. Human glioblastoma is the most frequent and aggressive type of brain tumors. The preferential expression of membrane protein connexin 43 (Cx43) and brain-specific anion transporter (BSAT1) in the tumor and peritumoral area is a key component for targeted drug delivery. The purpose of this study was to design cisplatin-loaded nanogels conjugated with monoclonal antibodies to Cx43 and BSAT1 for treatment of intracranial gliomas 101/8. MRI volumetric analysis of tumor-bearing rats indicated significantly reduced tumor volume with cisplatin-loaded targeted-nanogel treatment compared to other formulations. The median survival of rats treated with targeted nanogels conjugated with specific mAbs against extracellular loops of Cx43 and BSAT1 were 27 and 26.6 days higher than that in control group, respectively. For the first time we demonstrated the efficiency of mAb-targeted cisplatin-loaded nanogels in the experimental model of glioma 101/8. This approach could facilitate the development of new drug delivery systems for the treatment of gliomas.