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

Author:

Baiu Dana C1,Artz Nathan S2,McElreath Meghan R1,Menapace Bryan D1,Hernando Diego2,Reeder Scott B2,Grüttner Cordula3,Otto Mario1

Affiliation:

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

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

3. Micromod Partikeltechnologie GmbH, 18119 Rostock, Germany

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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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