Paramagnetic albumin decorated CuInS2/ZnS QDs for CD133(+) glioma bimodal MR/fluorescence targeted imaging

Paramagnetic albumin decorated CuInS2/ZnS QDs for CD133(+) glioma bimodal MR/fluorescence targeted imaging
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顺磁性白蛋白修饰的 CuInS2/ZnS QDs 用于 CD133( ) 胶质瘤双模态 MR/荧光靶向成像

DOI:
10.1039/c6tb00834h
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发表时间:
2016
影响因子:
7
通讯作者:
Zhang Bingbo
Zhang Bingbo
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhang Jing;Hao Guangyu;Yao Chenfei;Hu Su;Hu Chunhong;Zhang Bingbo

文献摘要

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胶质瘤干细胞(Glioma stem cells, GSCs)被认为是脑肿瘤发生、发展、侵袭、复发和治疗敏感性的关键。因此,利用探针在体内对GSCs进行精确的分子成像成为解决上述问题的前提。本文报道了一种敏感、特异、准确且具有生物相容性的分子纳米探针,采用MR/荧光成像方式用于CD133+胶质瘤双峰靶向成像。合成了高质量的CuInS2/ZnS核壳量子点(QDs),用于荧光成像;制备了具有Gd3+螯合的dtpa偶联BSA (BSA- dtpagd),并将其用于疏水性CuInS2/ZnS量子点的相转移和MR成像方式。然后将得到的亲水顺磁量子点(pQDs)与抗cd133单克隆抗体(pQDs - cd133mab,表示整个分子探针的框架)连接,用于靶向肿瘤。获得的pQDs-CD133mAb具有合适的尺寸(约45 nm)和良好的胶体稳定性。与商用Magnevist (r1 = 3.12 mM−1 s−1)相比,它具有高质量的荧光发射(约630 nm)和高纵向弛度(r1 = 15.2 mM−1 s−1)。体外和体内双模态成像显示pQDs-CD133mAb有效增强肿瘤。一项生物分布研究表明,pQDs-CD133mAb对肝胆和肾脏的作用没有明显的毒性。因此,pQDs-CD133mAb具有双模成像和靶向策略,具有作为胶质瘤准确诊断替代方案的巨大潜力。
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 CuInS2/ZnS core/shell quantum dots (QDs) were synthesized for fluorescence imaging; DTPA-coupled BSA with Gd3+ chelation (BSA-DTPAGd) were prepared and used both for phase transfer of hydrophobic CuInS2/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 (r1 = 15.2 mM−1 s−1) compared with that of commercial Magnevist (r1 = 3.12 mM−1 s−1). 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.