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用于脑肿瘤MRI可视化的VEGF靶向磁性纳米颗粒

VEGF-targeted magnetic nanoparticles for MRI visualization of brain tumor.

作者信息

Abakumov Maxim A, Nukolova Natalia V, Sokolsky-Papkov Marina, Shein Sergey A, Sandalova Tatiana O, Vishwasrao Hemant M, Grinenko Nadezhda F, Gubsky Iliya L, Abakumov Artem M, Kabanov Alexander V, Chekhonin Vladimir P

机构信息

Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia; Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, Russia.

Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Moscow, Russia; Division of Fundamental and Applied Neurobiology, Serbsky State Research Center of Social and Forensic Psychiatry, Moscow, Russia; Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Moscow, Russia.

出版信息

Nanomedicine. 2015 May;11(4):825-33. doi: 10.1016/j.nano.2014.12.011. Epub 2015 Jan 31.

Abstract

UNLABELLED

This work is focused on synthesis and characterization of targeted magnetic nanoparticles as magnetic resonance imaging (МRI) agents for in vivo visualization of gliomas. Ferric oxide (Fe3O4) cores were synthesized by thermal decomposition and coated with bovine serum albumin (BSA) to form nanoparticles with Deff of 53±9nm. The BSA was further cross-linked to improve colloidal stability. Monoclonal antibodies against vascular endothelial growth factor (mAbVEGF) were covalently conjugated to BSA through a polyethyleneglycol linker. Here we demonstrate that 1) BSA coated nanoparticles are stable and non-toxic to different cells at concentration up to 2.5mg/mL; 2) conjugation of monoclonal antibodies to nanoparticles promotes their binding to VEGF-positive glioma С6 cells in vitro; 3) targeted nanoparticles are effective in MRI visualization of the intracranial glioma. Thus, mAbVEGF-targeted BSA-coated magnetic nanoparticles are promising MRI contrast agents for glioma visualization.

FROM THE CLINICAL EDITOR

This work focuses on synthesis and characterization of targeted magnetic nanoparticles as magnetic resonance imaging (МRI) agents for in vivo visualization of gliomas. The authors utilize the fact that high-grade gliomas have extensive areas of necrosis and hypoxia, which results in increased secretion of angiogenesis vascular endothelial growth factor (VEGF). Monoclonal antibodies against vascular endothelial growth factor (mAbVEGF) were covalently conjugated to crosslinked BSA coated ferric oxide (Fe3O4) nanoparticles. The results show that these targeted nanoparticles are effective in MRI visualization of the intracranial glioma and may provide a new and promising contrast agent.

摘要

未标注

本研究聚焦于靶向磁性纳米颗粒的合成与表征,该纳米颗粒作为磁共振成像(MRI)剂用于胶质瘤的体内可视化。通过热分解合成了三氧化二铁(Fe3O4)核,并包覆牛血清白蛋白(BSA)以形成有效直径为53±9nm的纳米颗粒。对BSA进行进一步交联以提高胶体稳定性。抗血管内皮生长因子单克隆抗体(mAbVEGF)通过聚乙二醇连接子与BSA共价偶联。在此我们证明:1)BSA包覆的纳米颗粒在浓度高达2.5mg/mL时对不同细胞稳定且无毒;2)单克隆抗体与纳米颗粒偶联可促进其在体外与VEGF阳性胶质瘤C6细胞结合;3)靶向纳米颗粒在颅内胶质瘤的MRI可视化中有效。因此,mAbVEGF靶向的BSA包覆磁性纳米颗粒有望成为用于胶质瘤可视化的MRI造影剂。

临床编辑评论

本研究聚焦于靶向磁性纳米颗粒的合成与表征,该纳米颗粒作为磁共振成像(MRI)剂用于胶质瘤的体内可视化。作者利用高级别胶质瘤有广泛坏死和缺氧区域这一事实,这导致血管生成血管内皮生长因子(VEGF)分泌增加。抗血管内皮生长因子单克隆抗体(mAbVEGF)与交联的BSA包覆三氧化二铁(Fe3O4)纳米颗粒共价偶联。结果表明,这些靶向纳米颗粒在颅内胶质瘤的MRI可视化中有效,可能提供一种新的、有前景的造影剂。

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