Bevacizumab and near infrared probe conjugated iron oxide nanoparticles for vascular endothelial growth factor targeted MR and optical imaging

Abstract

Vascular endothelial growth factor (VEGF) plays a pivotal role in the cascade of development and progression of cancers. Targeting this cancer hallmark is a logical strategy for imaging based cancer detection and monitoring the anti-angiogenesis treatment. Using Bevacizumab (Avastin®), which is a recombinant humanized monoclonal antibody directly against VEGF and an angiogenesis inhibitor, as a targeting ligand, a multimodal VEGF targeted molecular imaging probe was developed by conjugating near infrared dye (NIR830) labeled bevacizumab to magnetic iron oxide nanoparticles (IONP) for optical and magnetic resonance (MR) imaging of cancers over-expressing VEGF. The targeting effect of NIR830-bevacizumab-IONPs on VEGF over-expressing cells was investigated by receptor mediated cell uptake experiments and a blocking assay using VEGF over-expressing 4T1 breast cancer cells. Systemic administration of VEGF-targeted NIR830-bevacizumab-IONPs into mice bearing 4T1 breast tumors resulted in higher accumulation of targeting IONPs in tumors compared to non-targeted IONPs. Quantitative analysis of T₂-weighted MRI at 48 h post-injection revealed that the averaged percentage of signal intensity change in tumors treated with NIR830-bevacizumab-IONPs was 52.4 ± 11.0% compared to 26.9 ± 12.4% in controls treated with non-targeted IONPs. The results demonstrated the feasibility and efficacy of NIR830-bevacizumab-IONPs as a VEGF targeting dual-modality molecular imaging probe that can be potentially used for imaging of cancers with VEGF over-expression and delivery of bevacizumab for imaging guided anti-cancer treatment.