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通过对 Gd(III)螯合剂进行位点选择性连接,将 P22 病毒衣壳作为血管内磁共振 T1 对比剂偶联物。

Implementation of P22 viral capsids as intravascular magnetic resonance T1 contrast conjugates via site-selective attachment of Gd(III)-chelating agents.

机构信息

School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea.

出版信息

Biomacromolecules. 2013 Jul 8;14(7):2332-9. doi: 10.1021/bm400461j. Epub 2013 Jun 24.

DOI:10.1021/bm400461j
PMID:23758486
Abstract

P22 viral capsids and ferritin protein cages are utilized as templating macromolecules to conjugate Gd(III)-chelating agent complexes, and we systematically investigates the effects of the macromolecules' size and the conjugation positions of Gd(III)-chelating agents on the magnetic resonance (MR) relaxivities and the resulting image contrasts. The relaxivity values of the Gd(III)-chelating agent-conjugated P22 viral capsids (outer diameter: 64 nm) are dramatically increased as compared to both free Gd(III)-chelating agents and Gd(III)-chelating agent-conjugated ferritins (outer diameter: 12 nm), suggesting that the large sized P22 viral capsids exhibit a much slower tumbling rate, which results in a faster T1 relaxation rate. Gd(III)-chelating agents are attached to either the interior or exterior surface of P22 viral capsids and the conjugation positions of Gd(III)-chelating agents, however, do not have a significant effect on the relaxivity values of the macromolecular conjugates. The contrast enhancement of Gd(III)-chelating agent-conjugated P22 viral capsids is confirmed by in vitro phantom imaging at a short repetition times (TR) and the potential usage of Gd(III)-chelating agent-conjugated P22 viral capsids for in vivo MR imaging is validated by visualizing a mouse's intravascular system, including the carotid, mammary arteries, the jugular vein, and the superficial vessels of the head at an isotropic resolution of 250 μm.

摘要

P22 病毒衣壳和铁蛋白蛋白笼被用作模板大分子,将 Gd(III)-螯合剂复合物连接起来,我们系统地研究了大分子的大小和 Gd(III)-螯合剂的连接位置对磁共振(MR)弛豫率和由此产生的图像对比度的影响。与游离 Gd(III)-螯合剂和 Gd(III)-螯合剂偶联铁蛋白(外径:12nm)相比,Gd(III)-螯合剂偶联 P22 病毒衣壳(外径:64nm)的弛豫率值显著增加,这表明大尺寸的 P22 病毒衣壳表现出较慢的翻滚率,导致更快的 T1 弛豫率。Gd(III)-螯合剂连接到 P22 病毒衣壳的内部或外部表面,并且 Gd(III)-螯合剂的连接位置对大分子缀合物的弛豫率值没有显著影响。通过在短重复时间(TR)的体外体模成像证实了 Gd(III)-螯合剂偶联 P22 病毒衣壳的对比增强,并且通过可视化包括颈动脉、乳腺动脉、颈静脉和头部的浅血管在内的小鼠的血管系统,验证了 Gd(III)-螯合剂偶联 P22 病毒衣壳在体内磁共振成像中的潜在用途,分辨率为 250μm。

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