Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People's Republic of China,
School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, People's Republic of China,
Int J Nanomedicine. 2018 Aug 10;13:4607-4625. doi: 10.2147/IJN.S168660. eCollection 2018.
BACKGROUND: The development of T-T dual contrast agent (CA) favors the visualization of the lesion in a more accurate and reliable manner by magnetic resonance imaging (MRI). The relaxivity and the interference between T and T CA are the main concerns for their design. METHODS: In this work, we constructed an FeO@mSiO/PDDA/BSA-GdO nanocomplex where BSA-GdO NPs and FeO NPs were chosen as T and T MRI CAs and a 20 nm mesoporous silica (mSiO) nanoshell was introduced to reduce the interference between them. We performed transmis sion electron microscopy, X-ray powder diffraction, UV-vis absorption spectra, and Fourier transform infrared absorption (FTIR) spectra to characterize the prepared nanocom-plex and MRI scanning to evaluate their MRI behaviors. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and hematologic and biochemical analyses were introduced to evaluate their in vitro and in vivo toxicity. Finally, the specific MRI of 786-0 cells with FeO@mSiO/PDDA/BSA-GdO-AS1411 nanoprobe in vitro was realized. In vivo biodistribution of FeO@mSiO/PDDA/BSA-GdO nanocomplex in the mouse was determined by the quantification of the Gd element by inductively coupled plasma-mass spectrometry. RESULTS: The prepared FeO@mSiO/PDDA/BSA-GdO nanocomplex possessed high longitudinal (=11.47 mM s Gd) and transverse (=195.1 mM s Fe) relaxivities, enabling its use as a T-T dual contrast agent for MRI. MTT testing and hematologic and biochemical analysis indicated the good biocompatibility of FeO@mSiO/PDDA/BSA-GdO nanocomplex in vitro and in vivo. After further conjugation with AS1411 aptamer, they could target tumor cells successfully by T and T MRI in vitro. The possible metabolic pathway of the tail vein-injected FeO@mSiO/PDDA/BSA-GdO nanocomplex in mouse was mainly via kidney. CONCLUSION: A T-T dual-mode contrast agent, FeO@mSiO/PDDA/BSA-GdO nano-complex, was developed and its good performance for tumor cell targeting in vitro and kidney contrast-enhanced MRI in mice indicated its promising potential as an effective T-T dual-mode contrast agent for in vivo MRI with self-confirmation.
背景：T-T 双对比剂（CA）的发展有利于通过磁共振成像（MRI）更准确、可靠地显示病变。弛豫率和 T 和 T CA 之间的干扰是其设计的主要关注点。
方法：在这项工作中，我们构建了一种 FeO@mSiO/PDDA/BSA-GdO 纳米复合物，其中选择 BSA-GdO NPs 和 FeO NPs 作为 T 和 T MRI CA，并引入 20nm 介孔硅（mSiO）纳米壳来减少它们之间的干扰。我们通过透射电子显微镜、X 射线粉末衍射、紫外可见吸收光谱和傅里叶变换红外吸收（FTIR）光谱对制备的纳米复合物进行了表征，并进行了 MRI 扫描以评估它们的 MRI 行为。此外，还引入了 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定和血液学及血液生化分析，以评估其体外和体内毒性。最后，通过体外 786-0 细胞与 FeO@mSiO/PDDA/BSA-GdO-AS1411 纳米探针的特异性 MRI 实现了 FeO@mSiO/PDDA/BSA-GdO 纳米探针的特异性 MRI。通过电感耦合等离子体质谱法（ICP-MS）定量测定 Gd 元素，确定 FeO@mSiO/PDDA/BSA-GdO 纳米复合物在小鼠体内的分布。
结果：制备的 FeO@mSiO/PDDA/BSA-GdO 纳米复合物具有较高的纵向（=11.47mM s Gd）和横向（=195.1mM s Fe）弛豫率，可作为 T-T 双对比剂用于 MRI。MTT 测试和血液学及血液生化分析表明，FeO@mSiO/PDDA/BSA-GdO 纳米复合物在体外和体内具有良好的生物相容性。进一步与 AS1411 适配体偶联后，它们能够通过体外 T 和 T MRI 成功靶向肿瘤细胞。静脉注射 FeO@mSiO/PDDA/BSA-GdO 纳米复合物在小鼠体内的可能代谢途径主要通过肾脏。
结论：开发了一种 T-T 双模造影剂 FeO@mSiO/PDDA/BSA-GdO 纳米复合物，其在体外对肿瘤细胞靶向性和在小鼠肾脏增强 MRI 中的良好性能表明，它作为一种有效的 T-T 双模造影剂，具有自我证实的体内 MRI 应用潜力。
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