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用于CD133胶质瘤双模态磁共振/荧光靶向成像的顺磁性白蛋白修饰的CuInS/ZnS量子点

Paramagnetic albumin decorated CuInS/ZnS QDs for CD133 glioma bimodal MR/fluorescence targeted imaging.

作者信息

Zhang Jing, Hao Guangyu, Yao Chenfei, Hu Su, Hu Chunhong, Zhang Bingbo

机构信息

Imaging Center, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

出版信息

J Mater Chem B. 2016 Jun 21;4(23):4110-4118. doi: 10.1039/c6tb00834h. Epub 2016 May 23.

Abstract

Glioma stem cells (GSCs) are considered the key to the occurrence, development, invasion, recurrence and sensitivity to treatment of brain tumors. Precise molecular imaging of GSCs by means of probes in vivo has therefore become a premise of solving the above problems. Herein, a sensitive, specific, accurate and biocompatible molecular nanoprobe is reported with MR/fluorescence imaging modalities for CD133 glioma tumor bimodal targeted imaging. Cd-free high quality CuInS/ZnS core/shell quantum dots (QDs) were synthesized for fluorescence imaging; DTPA-coupled BSA with Gd chelation (BSA-DTPA) were prepared and used both for phase transfer of hydrophobic CuInS/ZnS QDs and MR imaging modality. The resulting hydrophilic paramagnetic QDs (pQDs) were then linked with anti-CD133 monoclonal antibody, pQDs-CD133mAb denoting the framework of the entire molecular probe, for tumor targeting. The obtained pQDs-CD133mAb has a proper size (ca. 45 nm) and good colloidal stability. It exhibits a high quality fluorescent emission (ca. 630 nm) together with high longitudinal relaxivity (r = 15.2 mM s) compared with that of commercial Magnevist (r = 3.12 mM s). Dual modal imaging in vitro and in vivo shows potent tumor enhancement with administration of pQDs-CD133mAb. A biodistribution study indicates hepatobiliary and renal processing of pQDs-CD133mAb with no obvious toxicity. It could be therefore concluded, with a dual-modal imaging and targeting strategy, pQDs-CD133mAb presents a great potential as an alternative for accurate diagnosis of glioma.

摘要

胶质瘤干细胞(GSCs)被认为是脑肿瘤发生、发展、侵袭、复发及治疗敏感性的关键所在。因此,借助探针在体内对GSCs进行精确的分子成像已成为解决上述问题的前提。本文报道了一种灵敏、特异、准确且具有生物相容性的分子纳米探针,其具备用于CD133胶质瘤肿瘤双模态靶向成像的磁共振/荧光成像模式。合成了无镉的高质量CuInS/ZnS核壳量子点(QDs)用于荧光成像;制备了与钆螯合的二乙三胺五乙酸偶联牛血清白蛋白(BSA-DTPA),其既用于疏水性CuInS/ZnS QDs的相转移,又用于磁共振成像模式。然后将所得的亲水性顺磁性量子点(pQDs)与抗CD133单克隆抗体连接,pQDs-CD133mAb代表整个分子探针的结构框架,用于肿瘤靶向。所获得的pQDs-CD133mAb具有合适的尺寸(约45纳米)和良好的胶体稳定性。与市售的马根维显(r = 3.12 mM s)相比,它表现出高质量的荧光发射(约630纳米)以及高纵向弛豫率(r = 15.2 mM s)。体外和体内的双模态成像显示,给予pQDs-CD133mAb后肿瘤增强效果显著。一项生物分布研究表明,pQDs-CD133mAb经肝胆和肾脏代谢,且无明显毒性。因此可以得出结论,通过双模态成像和靶向策略,pQDs-CD133mAb作为胶质瘤精确诊断的替代方法具有巨大潜力。

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