A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging
A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging
复制标题
用于增强肝胆磁共振成像的肝细胞靶向纳米颗粒
DOI：
10.1038/s41551-022-00975-2
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发表时间：
2022
影响因子：
28.1
通讯作者：
Haiming Fan
中科院分区：
文献类型：
--
作者：
Huan Zhang;Yingkun Guo;Ju Jiao;Ying Qiu;Yuqing Miao;Yuan He;Zhenlin Li;Chunchao Xia;Li Li;Jing Cai;Ke Xu;Xiaoli Liu;Ce Zhang;Boon-Huat Bay;Shijie Song;Yanlian Yang;Mingli Peng;Yaoyu Wang;Haiming Fan
肝胆磁共振成像（MRI）可以为肝硬化和肝炎患者的肝脏肿瘤诊断提供信息。然而，由于缺乏敏感和特异性的造影剂，其临床应用受到阻碍，部分原因是肝细胞特异性纳米颗粒，无论其表面配体如何，都容易被枯否细胞隔离。在这里，我们表明，在兔，猪和猕猴，肝胆MRI的性能可以增强由锰铁氧体核心（直径3 nm）和聚（乙二醇）-乙氧基-苄基表面配体结合肝细胞特异性跨膜金属和阴离子转运蛋白组成的超小纳米粒子。与临床使用的造影剂钆塞酸二钠相比，纳米颗粒促进了更快，更灵敏和更高分辨率的肝胆MRI，大大提高了兔早期肝脏肿瘤的检出率（92%对48%），并更准确地评估了猕猴的胆道梗阻。纳米颗粒的性能和生物相容性支持肝脏特异性MRI造影剂的进一步转化开发。
Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle’s performance and biocompatibility support the further translational development of liver-specific MRI contrast agents.