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使用多功能抗GD2氧化铁纳米颗粒对人神经母细胞瘤进行高特异性靶向和检测。

High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles.

作者信息

Baiu Dana C, Artz Nathan S, McElreath Meghan R, Menapace Bryan D, Hernando Diego, Reeder Scott B, Grüttner Cordula, Otto Mario

机构信息

Department of Pediatrics, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53706, USA.

Department of Radiology, Medical Physics, Biomedical Engineering, Medicine & Emergency Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.

出版信息

Nanomedicine (Lond). 2015 Oct;10(19):2973-2988. doi: 10.2217/nnm.15.138. Epub 2015 Sep 30.

Abstract

AIM

To develop biocompatible, tumor-specific multifunctional iron-oxide nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy.

MATERIALS & METHODS: Clinical-grade humanized monoclonal antibody (hu14.18K322A), designed to target GD2 antigen on neuroblastoma with reduced nonspecific immune interactions, was conjugated to hydroxyethyl starch-coated iron-oxide nanoparticles. Targeting capability in vitro and in vivo was assessed by immunofluorescence, electron microscopy, analytical spectrophotometry, histochemistry and magnetic resonance R2* relaxometry.

RESULTS

The biocompatible nanoconstructs demonstrated high tumor specificity in vitro and in vivo, and low background uptake in a mouse flank xenograft model. Specific accumulation in tumors enabled particle visualization and quantification by magnetic resonance R2* mapping.

CONCLUSION

Our findings support the further development toward clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2-positive malignancies.

摘要

目的

开发针对神经母细胞瘤(一种侵袭性儿童恶性肿瘤)的具有生物相容性、肿瘤特异性的多功能氧化铁纳米结构。

材料与方法

设计用于靶向神经母细胞瘤上GD2抗原且非特异性免疫相互作用减少的临床级人源化单克隆抗体(hu14.18K322A)与羟乙基淀粉包被的氧化铁纳米颗粒偶联。通过免疫荧光、电子显微镜、分析分光光度法、组织化学和磁共振R2*弛豫测量法评估体外和体内的靶向能力。

结果

生物相容性纳米结构在体外和体内均表现出高肿瘤特异性,在小鼠侧腹异种移植模型中的背景摄取较低。肿瘤中的特异性积聚使得通过磁共振R2*成像能够对颗粒进行可视化和定量分析。

结论

我们的研究结果支持将这种抗GD2氧化铁纳米结构进一步开发用于临床,作为神经母细胞瘤以及潜在的其他GD2阳性恶性肿瘤的诊断和治疗支架。

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