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透明质酸功能化单壁碳纳米管作为肿瘤靶向磁共振成像造影剂。

Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent.

作者信息

Hou Lin, Zhang Huijuan, Wang Yating, Wang Lili, Yang Xiaomin, Zhang Zhenzhong

机构信息

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Jul 16;10:4507-20. doi: 10.2147/IJN.S78563. eCollection 2015.

Abstract

A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.

摘要

一种肿瘤靶向载体,即透明质酸(HA)功能化的单壁碳纳米管(SWCNTs),被用于专门递送靶向肿瘤细胞的磁共振成像(MRI)造影剂(CAs)。在该系统中,通过酰胺化过程可简单实现对SWCNTs的HA表面修饰,使这种纳米材料具有高度亲水性。通过细胞摄取实验评估了HA-SWCNTs对肿瘤细胞的细胞内转运能力,由于HA的存在,摄取顺序为HA-SWCNTs>SWCNTs,流式细胞术也证实了这一点。对这种MRI造影剂进行了体外和体内安全性评估。结果表明,HA-SWCNTs可作为生物相容性纳米载体,与游离的GdCl3相比,钆(Gd)/HA-SWCNTs几乎没有毒性。此外,负载GdCl3的HA-SWCNTs可显著延长MRI的循环时间。最后,为了研究Gd/HA-SWCNTs的MRI造影增强能力,采集了荷瘤小鼠的T1加权MR图像。结果表明,Gd/HA-SWCNTs具有最高的肿瘤靶向效率和T1弛豫率增强效果,表明HA-SWCNTs可被开发为一种肿瘤靶向载体,用于递送造影剂GdCl3,以实现肿瘤的可识别诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3908/4509541/b53b9c9f4530/ijn-10-4507Fig1.jpg

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