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

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.

Keywords: MRI; anti-GD2; cancer; iron-oxide nanoparticle; neuroblastoma; pediatric; tumor targeted.