Baklaushev Vladimir P, Nukolova Natalia N, Khalansky Alexander S, Gurina Olga I, Yusubalieva Gaukhar M, Grinenko Nadejhda Ph, Gubskiy Ilya L, Melnikov Pavel A, Kardashova Karina Sh, Kabanov Alexander V, Chekhonin Vladimir P
Department of Medicinal Nanobiotechnology, Pirogov Russian State Medical University , Moscow , Russia .
Drug Deliv. 2015 May;22(3):276-85. doi: 10.3109/10717544.2013.876460. Epub 2014 Jan 17.
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.
用于脑肿瘤治疗的靶向给药是纳米医学的重要目标之一。人类胶质母细胞瘤是最常见且侵袭性最强的脑肿瘤类型。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Cx43和BSAT1单克隆抗体偶联的载顺铂纳米凝胶,用于治疗颅内胶质瘤101/8。对荷瘤大鼠的MRI体积分析表明,与其他制剂相比,载顺铂靶向纳米凝胶治疗可显著降低肿瘤体积。用针对Cx43和BSAT1细胞外环的特异性单克隆抗体偶联的靶向纳米凝胶治疗的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实验模型中证明了单克隆抗体靶向载顺铂纳米凝胶的有效性。这种方法有助于开发用于治疗胶质瘤的新型给药系统。