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用于肝细胞癌靶向CT/MR双模态成像的透明质酸修饰的锰螯合树枝状大分子包裹金纳米颗粒

Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma.

作者信息

Wang Ruizhi, Luo Yu, Yang Shuohui, Lin Jiang, Gao Dongmei, Zhao Yan, Liu Jinguo, Shi Xiangyang, Wang Xiaolin

机构信息

Shanghai Institute of Medical Imaging, Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China.

出版信息

Sci Rep. 2016 Sep 22;6:33844. doi: 10.1038/srep33844.

DOI:10.1038/srep33844
PMID:27653258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5032118/
Abstract

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au)G5.NH-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au)G5.NH-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au)G5.NH-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.

摘要

肝细胞癌（HCC）是肝脏最常见的恶性肿瘤。人们一直渴望实现早期有效的诊断。在此，我们展示了用于计算机断层扫描（CT）/磁共振（MR）双模成像的、靶向表达CD44受体的癌细胞的透明质酸（HA）修饰多功能纳米颗粒（NPs）的制备与表征。我们首先用锰螯合剂1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）、异硫氰酸荧光素（FI）和HA对末端为胺基的第5代聚（酰胺胺）树枝状大分子（G5.NH）进行修饰。然后，将金纳米颗粒（AuNPs）包裹在上述产物中，记为G5.NH-FI-DOTA-HA。经过进一步的锰螯合和纯化后形成了设计的多功能NPs，记为{(Au)G5.NH-FI-DOTA(Mn)-HA}。这些NPs通过几种不同技术进行了表征。我们发现{(Au)G5.NH-FI-DOTA(Mn)-HA} NPs表现出良好的水分散性、在不同条件下的稳定性以及在给定浓度范围内的细胞相容性。由于产物中同时存在AuNPs和锰，{(Au)G5.NH-FI-DOTA(Mn)-HA}显示出高X射线衰减强度和良好的r弛豫率，这些都是靶向CT/MR双模成像的有利特性。该方法通过CD44受体介导的内吞途径用于体外对HCC细胞成像以及在独特的体内模型中对原位移植的HCC肿瘤成像。这项工作介绍了一种通过树枝状大分子纳米技术制备多功能NPs的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/958f38a588db/srep33844-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/b1eb0478efc7/srep33844-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/58ebd8a0dcc3/srep33844-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/717f88a2c405/srep33844-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/4c21c4aa2cf7/srep33844-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/4d248e9d8da2/srep33844-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/a934137b5b1b/srep33844-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/15f8aaec86be/srep33844-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/1efc0754837c/srep33844-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/958f38a588db/srep33844-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/b1eb0478efc7/srep33844-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/58ebd8a0dcc3/srep33844-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/717f88a2c405/srep33844-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/4c21c4aa2cf7/srep33844-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/4d248e9d8da2/srep33844-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/a934137b5b1b/srep33844-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/15f8aaec86be/srep33844-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/1efc0754837c/srep33844-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/5032118/958f38a588db/srep33844-f9.jpg

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