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

使用多功能抗GD2氧化铁纳米粒子对人类神经母细胞瘤进行高特异性靶向和检测

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

Aim

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

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.

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.

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