Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer
Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer
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DOI：
10.1016/j.biomaterials.2010.02.068
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发表时间：
2010-06-01
期刊：
影响因子：
14
通讯作者：
Hong, Soon-Sun
中科院分区：
文献类型：
--
作者：
Maeng, Jin Hee;Lee, Don-Haeng;Hong, Soon-Sun
为了开发一种具有增强疗效和最小副作用的药物递送系统，我们合成了一种新型的聚合物纳米粒（YCC-DOX），其由聚（环氧乙烷）-偏苯三酸酐氯化物-叶酸（PEO-TMA-FA）、多柔比星（DOX）和超顺磁性氧化铁（Fe 3 O 4）和叶酸组成。在患有肝癌的大鼠和兔子中，与游离DOX（FD）和商业脂质体药物DOXIL（R）相比，评估了纳米颗粒的功效。YCC-DOX显示出抗癌功效和特异性靶向表达叶酸受体（FR）的肿瘤，从而增加DOX的生物利用度和功效。在大鼠和兔模型中，与FD和DOXIL（R）组相比，YCC-DOX组的相对肿瘤体积分别减少了2倍和4倍。此外，YCC-DOX显示出比常规MRI造影剂（Resovist（R））更高的MRI灵敏度，即使其铁含量较低。免疫组化显示，YCC-DOX组血管生成标志物CD 34和细胞增殖标志物Ki-67的表达较低，而末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法显示，YCC-DOX组凋亡细胞明显增多。这些结果表明，YCC-DOX是治疗肝癌和使用MRI监测癌症进展的有希望的候选物。皇冠版权所有（C）2010由爱思唯尔有限公司出版。保留所有权利。
To develop a drug delivery system with enhanced efficacy and minimized adverse effects, we synthesized a novel polymeric nanoparticles, (YCC-DOX) composed of poly (ethylene oxide)-trimellitic anhydride chloride-folate (PEO-TMA-FA), doxorubicin (DOX) and superparamagnetic iron oxide (Fe3O4) and folate. The efficacy of the nanoparticles was evaluated in rats and rabbits with liver cancer, in comparison with free-DOX (FD) and a commercial liposome drug, DOXIL(R). YCC-DOX showed the anticancer efficacy and specifically targeted folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of DOX. The relative tumor volume of the YCC-DOX group was decreased two- and four-fold compared with the FD and DOXIL(R) groups in the rat and rabbit models, respectively. Furthermore, YCC-DOX showed higher MRI sensitivity comparable to a conventional MRI contrast agent (Resovist(R)), even in its lower iron content. In the immunohistochemical analysis, YCC-DOX group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC-DOX group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. These results indicate that YCC-DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.