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Bcl-2 功能化的超顺磁性氧化铁纳米颗粒被两亲聚合物包被,提高了胰岛的标记效率,可用于磁共振成像检测。

Bcl-2-functionalized ultrasmall superparamagnetic iron oxide nanoparticles coated with amphiphilic polymer enhance the labeling efficiency of islets for detection by magnetic resonance imaging.

机构信息

Department of Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

出版信息

Int J Nanomedicine. 2013;8:3977-90. doi: 10.2147/IJN.S52058. Epub 2013 Oct 16.

Abstract

Based on their versatile, biocompatible properties, superparamagnetic iron oxide (SPIO) or ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are utilized for detecting and tracing cells or tumors in vivo. Here, we developed an innoxious and concise synthesis approach for a novel B-cell lymphoma (Bcl)-2 monoclonal antibody-functionalized USPIO nanoparticle coated with an amphiphilic polymer (carboxylated polyethylene glycol monooleyl ether [OE-PEG-COOH]). These nanoparticles can be effectively internalized by beta cells and label primary islet cells, at relatively low iron concentration. The biocompatibility and cytotoxicity of these products were investigated by comparison with the commercial USPIO product, FeraSpin(™) S. We also assessed the safe dosage range of the product. Although some cases showed a hypointensity change at the site of transplant, a strong magnetic resonance imaging (MRI) was detectable by a clinical MRI scanner, at field strength of 3.0 Tesla, in vivo, and the iron deposition/attached in islets was confirmed by Prussian blue and immunohistochemistry staining. It is noteworthy that based on our synthesis approach, in future, we could exchange the Bcl-2 with other probes that would be more specific for the targeted cells and that would have better labeling specificity in vivo. The combined results point to the promising potential of the novel Bcl-2-functionalized PEG-USPIO as a molecular imaging agent for in vivo monitoring of islet cells or other cells.

摘要

基于多功能、生物相容性的特性,超顺磁性氧化铁(SPIO)或超超顺磁性氧化铁(USPIO)纳米粒子被用于体内检测和追踪细胞或肿瘤。在此,我们开发了一种新颖的无毒且简洁的合成方法,用于制备新型 B 细胞淋巴瘤(Bcl)-2 单克隆抗体功能化的 USPIO 纳米粒子,该纳米粒子由两亲聚合物(羧基化聚乙二醇单油醚[OE-PEG-COOH])包裹。这些纳米粒子可以在相对较低的铁浓度下被β细胞有效内化,并标记原代胰岛细胞。通过与商业 USPIO 产品 FeraSpin(™) S 进行比较,研究了这些产物的生物相容性和细胞毒性。我们还评估了该产品的安全剂量范围。尽管有些情况下在移植部位出现了低信号强度改变,但在 3.0 特斯拉的场强下,通过临床 MRI 扫描仪可以检测到强烈的磁共振成像(MRI),并且可以通过普鲁士蓝和免疫组织化学染色来证实铁在胰岛中的沉积/附着。值得注意的是,基于我们的合成方法,在未来,我们可以用其他探针来取代 Bcl-2,这些探针对于靶向细胞更具特异性,并且在体内具有更好的标记特异性。综合结果表明,新型 Bcl-2 功能化的 PEG-USPIO 作为一种分子成像剂,具有用于体内监测胰岛细胞或其他细胞的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bd/3804583/ac812639cbc5/ijn-8-3977Fig1.jpg

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