Design of 99mTc-Labeled Low Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted Single Photon Emission Computed Tomography/Computed Tomography Imaging of Gliomas
Design of 99mTc-Labeled Low Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted Single Photon Emission Computed Tomography/Computed Tomography Imaging of Gliomas
复制标题
用于胶质瘤靶向单光子发射计算机断层扫描/计算机断层扫描成像的 99mTc 标记低代树枝状聚合物包埋金纳米颗粒的设计
DOI：
10.1166/jbn.2019.2760
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发表时间：
2019-06-01
影响因子：
2.9
通讯作者：
Zhao, Jinhua
中科院分区：
文献类型：
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作者：
Li, Yujie;Zhao, Lingzhou;Zhao, Jinhua
趋化因子受体-4(CXCR4)在胶质瘤细胞中高表达，与预后不良有关。在本研究中，我们设计并合成了标记的低世代树枝状大分子包裹的金纳米粒子(Au-DENPs)，并将其修饰为CXCR4-配体，用于脑胶质瘤的靶向单光子发射计算机断层扫描(SPECT/CT)成像。将第二代聚酰胺胺树枝状大分子依次与二乙三胺五乙酸乙酯(DTPA)和CXCR4特异性配体FC131肽修饰的聚乙二醇单乙二醇组分偶联，并以此为模板制备了金纳米颗粒。将~(99m)Tc通过DTPA络合标记后，制备了靶向脑胶质瘤SPECT/CT双模纳米探针{(Au-0)(6)-G2-TC-99m-DTPA-(PEG-FC131)}DENPs。对标记前后的FC131功能化Au-DENP进行了较好的表征。结果表明，在~(131)Tc标记前，FC131功能化的Au-DENPs具有均匀的尺寸分布，在给定的Au浓度范围内具有良好的生物相容性，并且由于FC131的附着，可以特异性地靶向胶质瘤细胞。此外，FC131功能化的Au-DENPs可以很容易地被~(99)T标记，具有良好的放化稳定性和较高的放化纯度。[(Au-0)(6)-G2-TC-99m-DTPA-(PEG-FC131)]DENPs在体外和皮下肿瘤模型中对脑胶质瘤细胞的靶向SPECT/CT显像效果良好。所开发的FC131功能化树枝状大分子纳米探针可能在不同CXCR4过表达肿瘤的SPECT/CT成像中具有很大的潜力。
Chemokine receptor-4 (CXCR4) has been demonstrated to be overexpressed in glioma cells and associated with poor survival. In the present study, we designed and synthesized Tc-99m-labeled low-generation dendrimer-entrapped gold nanoparticles (Au DENPs), which were modified with CXCR4-ligand for targeted single photon emission computed tomography (SPECT)/computed tomography (CT) imaging of glioma. Generation two poly(amidoamine) dendrimers were sequentially conjugated with diethylenetriamine pentacetate acid (DTPA) and polyethylene glycol (PEG) modified with FC131 peptide (a CXCR4-specific ligand), and were then utilized as a template for entrapment of gold nanoparticles (Au NPs). After radiolabeling with Tc-99m via DTPA chelation, the glioma-targeting SPECT/CT dual mode nanoprobe {(Au-0)(6)-G2-Tc-99m-DTPA-(PEG-FC131)} DENPs were generated. The FC131-functionalized Au DENPs before and after Tc-99m radiolabeling were well characterized. The results revealed that prior to Tc-99m radiolabeling, FC131-functionalized Au DENPs had a uniform size distribution, acceptable biocompatibility in the given Au concentration range and could specifically target glioma cells due to the attached FC131. Furthermore, the FC131-functionalized Au DENPs could be readily radiolabeled by Tc-99m with good radiochemical stability and high radiochemical purity. The {(Au-0)(6)-G2-Tc-99m-DTPA-(PEG-FC131)) DENPs appeared to be effective in targeted SPECT/CT imaging of glioma cells in vitro and in vivo in a subcutaneous tumor model. The developed FC131-functionalized dendrimer-based nanoprobe may hold a great potential for utilization in SPECT/CT imaging of different CXCR4-overexpressing cancers.