The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI
The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI
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Exendin-4 缀合的超顺磁性氧化铁纳米颗粒在 β 细胞靶向 MRI 中的作用
DOI：
10.1016/j.biomaterials.2013.04.021
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发表时间：
2013-07-01
期刊：
影响因子：
14
通讯作者：
Wu, Yulian
中科院分区：
文献类型：
--
作者：
Zhang, Bo;Yang, Bin;Wu, Yulian
胰腺β细胞或胰岛的非侵入性靶向可视化正成为分子成像在糖尿病和胰岛移植研究中应用的重点，但由于缺乏特异性的β细胞生物标志物，目前这一研究并不成功。胰升糖素样肽1受体(GLP-1R)在β细胞中高表达，被认为是一个很有前途的靶点。我们利用GLP-1类似物-exendin-4与聚乙二醇包被的超顺磁性氧化铁(PEGSPIO)偶联，制备了一种靶向超顺磁性氧化铁(SPIO)纳米粒子。结果表明，Exendin-4功能化的SPIO能够与表达GLP-1R的INS-1细胞特异性结合并内化，其标记效率高于非靶向纳米粒。值得注意的是，SPIO-exendin4可以在体外区别标记胰腺切片或β细胞移植物中的胰岛。SPIO-exendin4在荷瘤裸鼠体内的全身给药胰岛素瘤(来源于INS-1细胞)导致纳米颗粒在肿瘤中积聚，产生临床MRI扫描仪在3.0T场强下可检测到的强烈磁共振成像对比度，普鲁士蓝染色进一步证实了肿瘤中的铁沉积。此外，初步的生物分布研究表明，Spio-exendin4有在胰腺中蓄积的趋势。毒性评价表明其具有良好的体内生物相容性。这些结果表明，SPIO-exendin4有可能作为分子靶向显像剂用于胰岛素瘤的体内成像，并可能用于未来的β细胞成像。(C)2013爱思唯尔有限公司。保留所有权利。
Noninvasive targeted visualization of pancreatic beta cells or islets is becoming the focus of molecular imaging application in diabetes and islet transplantation studies, but it is currently unsuccessful due to the lack of specific beta cell biomarkers. Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in beta cells and considered as a promising target. We here developed a targeted superparamagnetic iron oxide (SPIO) nanoparticle using GLP-1 analog-exendin-4 which is conjugated to polyethylene glycol coated SPIO (PEG-SPIO). The results demonstrated that exendin-4 functionalized SPIO was able to specifically bind to and internalized by GLP-1R-expressing INS-1 cells, with the higher labeling efficiency than non-targeted nanoparticles. Notably, SPIO-exendin4 could differentially label islets in pancreatic slices or beta cell grafts in vitro. Systemic delivery of SPIO-exendin4 into nude mice bearing s.c. insulinomas (derived from INS-1 cells) leads to the accumulation of the nanoparticles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical MRI scanner at field strength of 3.0 T, and the iron deposition in tumors was further confirmed by Prussian blue staining. Furthermore, preliminary biodistribution study indicated that SPIO-exendin4 had a tendency to accumulate in pancreas. Toxicity assessments demonstrated good biocompatibility in vivo. These results suggest that SPIO-exendin4 has potential as molecularly targeted imaging agents for in vivo imaging of insulinoma, and possibly for future beta cell imaging. (C) 2013 Elsevier Ltd. All rights reserved.