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Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles
Published on: October 19, 2015
Bevacizumab and near infrared probe conjugated iron oxide nanoparticles for vascular endothelial growth factor
Run Lin1, Jing Huang, Liya Wang
1Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
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.
Insights
A novel dual-modality imaging probe targets vascular endothelial growth factor (VEGF) in cancers. This probe, comprising iron oxide nanoparticles and an anti-VEGF antibody, shows enhanced tumor accumulation and improved MRI contrast for cancer detection and treatment monitoring.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Imaging
Background:
- Vascular endothelial growth factor (VEGF) is crucial in cancer development and progression.
- Targeting VEGF offers a strategy for cancer detection and anti-angiogenesis treatment monitoring.
- Developing effective molecular imaging probes is essential for precision oncology.
Purpose of the Study:
- To develop a multimodal imaging probe targeting VEGF for cancer detection.
- To evaluate the efficacy of the probe in imaging and monitoring anti-angiogenesis therapy.
- To assess the dual-modality capabilities (optical and MR imaging) of the developed probe.
Main Methods:
- Conjugation of a near-infrared dye (NIR830)-labeled anti-VEGF antibody (Bevacizumab) to iron oxide nanoparticles (IONPs).
- Investigation of targeted cell uptake using VEGF-overexpressing 4T1 breast cancer cells and blocking assays.
- In vivo studies in mice bearing 4T1 tumors to assess tumor accumulation via MRI and optical imaging.
Main Results:
- The NIR830-Bevacizumab-IONPs demonstrated receptor-mediated cell uptake in VEGF-overexpressing cells.
- Systemic administration led to higher accumulation of targeted IONPs in tumors compared to non-targeted IONPs.
- T2-weighted MRI showed a significant signal intensity change in tumors treated with targeted IONPs (52.4%) versus controls (26.9%).
Conclusions:
- NIR830-Bevacizumab-IONPs serve as a feasible and effective VEGF-targeting dual-modality molecular imaging probe.
- The probe shows potential for imaging VEGF-overexpressing cancers.
- This technology could enable imaging-guided anti-cancer treatment delivery.
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