Dana C Baiu1, Nathan S Artz2, Meghan R McElreath1, Bryan D Menapace1, Diego Hernando2, Scott B Reeder2, Cordula Grüttner3, Mario Otto1. 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.
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-GD2iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2-positive malignancies.
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