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用于肿瘤诊断的十克规模有机钆配合物纳米颗粒的简便合成

Ten-Gram-Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis.

作者信息

Wei Zhenni, Jiang Zhenqi, Pan Chunshu, Xia Jianbi, Xu Kaiwei, Xue Ting, Yuan Bo, Akakuru Ozioma Udochukwu, Zhu Chengjie, Zhang Guilong, Mao Zheng, Qiu Xiaozhong, Wu Aiguo, Shen Zheyu

机构信息

Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, 1219 Zhongguan West Road, Zhenhai District, Ningbo, Zhejiang, 315201, China.

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Baiyun District, Guangzhou, Guangdong, 510515, China.

出版信息

Small. 2020 Mar;16(11):e1906870. doi: 10.1002/smll.201906870. Epub 2020 Feb 24.

Abstract

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten-gram-scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd-salicylate nanoparticles, GdSalNPs-rBSA) with high r value of 19.51 mm s and very low r /r ratio of 1.21 (B = 1.5 T) for high-contrast T -weighted MRI of tumors. The GdSalNPs-rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t = 6.13 h), almost no Gd release, and excellent biosafety. Moreover, the GdSalNPs-rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal-to-noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.

摘要

几十年来,临床磁共振成像(MRI)可用的造影剂市场一直由基于钆(Gd)螯合物的T造影剂主导。然而,人们对其安全性的担忧日益增加,因为它们会滞留在体内且具有肾毒性,这使得美国食品药品监督管理局发出了关于此类造影剂使用的警告。为改善这些问题,有必要提高此类造影剂的MRI效率,以便能够大幅减少给药剂量。在本研究中,开发了一种十克规模的简便方法来合成有机钆复合纳米颗粒(即还原牛血清白蛋白稳定的钆 - 水杨酸盐纳米颗粒,GdSalNPs - rBSA),其具有19.51 mm s的高r值和1.21的极低r /r比率(B = 1.5 T),用于肿瘤的高对比度T加权MRI。GdSalNPs - rBSA纳米颗粒具有更多优势,包括合成成本低(约0.54美元/克)、体内循环时间长(t = 6.13 h)、几乎无钆释放以及出色的生物安全性。此外,GdSalNPs - rBSA纳米颗粒在肿瘤诊断的体内MRI对比增强方面表现出色(信噪比(ΔSNR)≈220%)。

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