Baiu Dana C, Artz Nathan S, McElreath Meghan R, Menapace Bryan D, Hernando Diego, Reeder Scott B, Grüttner Cordula, Otto Mario
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.
Nanomedicine (Lond). 2015 Oct;10(19):2973-2988. doi: 10.2217/nnm.15.138. Epub 2015 Sep 30.
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.
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.
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.
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。
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。
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。
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。
