EGFRvIII antibody-conjugated iron oxide nanoparticles for magnetic resonance imaging-guided convection-enhanced delivery and targeted therapy of glioblastoma.
EGFRvIII antibody-conjugated iron oxide nanoparticles for magnetic resonance imaging-guided convection-enhanced delivery and targeted therapy of glioblastoma.
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DOI：
10.1158/0008-5472.can-10-1022
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发表时间：
2010-08-01
期刊：
影响因子：
11.2
通讯作者：
Mao H
中科院分区：
文献类型：
--
作者：
Hadjipanayis CG;Machaidze R;Kaluzova M;Wang L;Schuette AJ;Chen H;Wu X;Mao H
磁性纳米颗粒已成为一种潜在的多功能临床工具，可以通过磁共振成像（MRI）对比度增强来检测癌细胞以及靶向癌细胞治疗。将纳米技术用于脑肿瘤应用的一个主要障碍是难以将纳米颗粒递送至颅内肿瘤。氧化铁纳米粒子（IONP；核心尺寸为 10 nm）与纯化抗体缀合，该抗体选择性结合人多形性胶质母细胞瘤（GBM）细胞上存在的表皮生长因子受体（EGFR）缺失突变体（EGFRvIII），用于实验性胶质母细胞瘤的体外和体内治疗靶向和 MRI 对比度增强。 对流增强输送（CED）。纳米颗粒处理后，观察到胶质母细胞瘤细胞存活率显着下降，而人星形胶质细胞处理后未观察到毒性（P<0.001）。 EGFRvIIIAb-IONP 治疗后，胶质母细胞瘤细胞中 EGFR 磷酸化降低。用 EGFRvIIIAb-IONP 处理 GBM 细胞和含有胶质母细胞瘤干细胞 (GSC) 的神经球后，细胞死亡被确定为细胞死亡的模式。 MRI 引导的 EGFRvIIIAb-IONP 的 CED 允许磁性纳米颗粒在颅内人类异种移植肿瘤内或附近进行初始分布，并在几天后继续分散。在植入高致瘤性胶质母细胞瘤异种移植物 (U87ΔEGFRvIII) 的小鼠中，使用磁性纳米颗粒进行 CED 后 (P<0.01)，动物存活率显着增加。 IONP与人胶质母细胞瘤组成型表达的EGFRvIII缺失突变体特异性抗体缀合，可以提供肿瘤细胞的选择性MRI对比增强以及CED后浸润性胶质母细胞瘤细胞的靶向治疗。
The magnetic nanoparticle has emerged as a potential multifunctional clinical tool that can provide cancer cell detection by magnetic resonance imaging (MRI) contrast enhancement as well as targeted cancer cell therapy. A major barrier in the use of nanotechnology for brain tumor applications is the difficulty in delivering nanoparticles to intracranial tumors. Iron oxide nanoparticles (IONPs; 10 nm in core size) conjugated to a purified antibody that selectively binds to the epidermal growth factor receptor (EGFR) deletion mutant (EGFRvIII) present on human glioblastoma multiforme (GBM) cells, were used for therapeutic targeting and MRI contrast enhancement of experimental glioblastoma both in vitro and in vivo after convection-enhanced delivery (CED). A significant decrease in glioblastoma cell survival was observed after nanoparticle treatment and no toxicity was observed with treatment of human astrocytes (P<0.001). Lower EGFR phosphorylation was found in glioblastoma cells after EGFRvIIIAb-IONP treatment. Apoptosis was determined to be the mode of cell death after treatment of GBM cells and glioblastoma stem cell (GSC)-containing neurospheres with EGFRvIIIAb-IONPs. MRI-guided CED of EGFRvIIIAb-IONPs allowed for the initial distribution of magnetic nanoparticles within or adjacent to intracranial human xenograft tumors and continued dispersion days later. A significant increase in animal survival was found after CED of magnetic nanoparticles (P<0.01) in mice implanted with highly tumorigenic glioblastoma xenografts (U87ΔEGFRvIII). IONPs conjugated to an antibody specific to the EGFRvIII deletion mutant constitutively expressed by human glioblastoma tumors can provide selective MRI contrast enhancement of tumor cells and targeted therapy of infiltrative glioblastoma cells after CED.