Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer
Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer
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DOI：
10.1016/j.biomaterials.2011.03.077
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发表时间：
2011-08-01
期刊：
影响因子：
14
通讯作者：
Zhang, Na
中科院分区：
文献类型：
--
作者：
Liu, Yongjun;Chen, Zhijin;Zhang, Na
分子影像学对于提高肿瘤诊断的敏感性和选择性，特别是在肿瘤的早期阶段是必不可少的。本研究设计了一种同时修饰Gd-DTPA和抗血管内皮生长因子（VEGF）抗体的新型多功能聚合物纳米粒子造影剂（Anti-VEGF PLA-PEG-PLL-Gd NP），将Gd-DTPA递送到肿瘤区域，实现肝癌的早期诊断。抗VEGF PLA-PEG-PLL-Gd纳米粒在实验浓度下对人肝癌细胞（HepG 2）具有较高的T-1弛豫率，且无明显的细胞毒性。体外细胞摄取实验结果表明，纳米粒的摄取过程具有浓度和时间依赖性。与非靶向纳米颗粒相比，抗VEGF抗体修饰的纳米颗粒在HepG 2细胞中显示出高得多的细胞摄取。在体内研究中，与非靶向NPs和Gd-DTPA注射组相比，靶向NPs在荷瘤小鼠肿瘤部位（小鼠肝癌肿瘤，H22）显示出显著的信号强度增强，成像时间从不到1 h（Gd-DTPA注射组）显著延长至12 h。这些结果表明，这种新型MRI造影剂Anti-VEGF PLA-PEG-PLL-Gd NPs在肝脏肿瘤的早期诊断中显示出巨大的潜力。(C)2011爱思唯尔有限公司保留所有权利。
Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T-1 relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors. (C) 2011 Elsevier Ltd. All rights reserved.