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

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Bevacizumab and near infrared probe conjugated iron oxide nanoparticles for vascular endothelial growth factor targeted MR and optical imaging†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-03-22 00:00:00 , DOI: 10.1039/c8bm00225h
Run Lin _{1,

2,

3,

4,

5} , Jing Huang _{6,

7,

8,

9} , Liya Wang _{1,

6,

7,

8,

9} , Yuancheng Li _{6,

7,

8,

9} , Malgorzata Lipowska _{6,

7,

8,

9} , Hui Wu _{6,

7,

8,

9} , Jianyong Yang _{1,

2,

3,

4,

5} , Hui Mao _{6,

7,

8,

9}

Affiliation

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.

中文翻译：

贝伐单抗和近红外探针偶联的氧化铁纳米粒子用于靶向血管内皮生长因子的MR和光学成像†

血管内皮生长因子（VEGF）在癌症的发展和进程中起着举足轻重的作用。瞄准这一癌症标志是用于基于成像的癌症检测和监测抗血管生成治疗的逻辑策略。使用直接针对VEGF和血管生成抑制剂的重组人源化单克隆抗体Bevacizumab（Avastin®）作为靶向配体，通过将近红外染料（NIR830）标记的bevacizumab与磁性氧化铁缀合，开发了多模式VEGF靶向分子成像探针。纳米粒子（IONP）用于过度表达VEGF的癌症的光学和磁共振（MR）成像。通过受体介导的细胞摄取实验和使用VEGF过表达的4T1乳腺癌细胞的阻断试验研究了NIR830-贝伐单抗-IONPs对VEGF过表达的细胞的靶向作用。与未靶向的IONP相比，将VEGF靶向的NIR830-贝伐单抗-IONPs全身给药于带有4T1乳腺肿瘤的小鼠体内，导致肿瘤中靶向IONP的积累更高。定量分析注射后48小时的T ₂加权MRI显示，使用NIR830-贝伐单抗-IONPs治疗的肿瘤的平均信号强度变化百分比为52.4±11.0％，而使用非靶向IONPs的对照组则为26.9±12.4％。结果表明，NIR830-贝伐单抗-IONPs作为靶向VEGF的双模态分子成像探针的可行性和功效，可潜在地用于对具有VEGF过表达和传递贝伐单抗的癌症进行成像，以进行成像指导的抗癌治疗。

更新日期：2018-03-22

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