Superparamagnetic iron oxide nanoparticles mediated (131)I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice.
Superparamagnetic iron oxide nanoparticles mediated (131)I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice.
复制标题
超顺磁性氧化铁纳米粒子介导的131I-hVEGF siRNA抑制裸鼠肝癌肿瘤生长
DOI：
10.1186/1471-2407-14-114
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发表时间：
2014-02-21
期刊：
影响因子：
3.8
通讯作者：
Xiong W
中科院分区：
文献类型：
--
作者：
Chen J;Zhu S;Tong L;Li J;Chen F;Han Y;Zhao M;Xiong W
背景
肝细胞癌是一种原发的肝脏肿瘤，是人类最难治疗的恶性肿瘤。在这项研究中，我们试图开发一种综合方法，在这种方法中，实时肿瘤监测、基因治疗和内部放射治疗可以同时进行。这是通过用超顺磁性氧化铁纳米颗粒(SPIO)携带带有放射性碘131(131I)的小干扰RNA对抗人血管内皮生长因子(HVEGF)来靶向肝细胞癌来实现的。
方法
通过Bolton-Hunter方法将hVEGFsiRNA标记为131I，并与SilenceMag(一种SPIO)偶联。然后将131I-hVEGFsiRNA/SilenceMag注射到暴露于外磁场(EMF)的裸鼠体内。通过SPECT(单光子发射计算机断层扫描)和MRI(磁共振成像)研究和血液动力学分析，评价131I-hVEGFsiRNA/SilenceMag的生物分布和细胞毒性。在为期4周的实验中，每天测量荷瘤裸鼠的体重和肿瘤体积。
结果
131I-hVEGF siRNA/SilenceMag标记成功，放化纯度(80%)和体外生物活性均令人满意。SPECT、MRI和生物分布研究表明，外用EMF成功地在肝癌肿瘤中吸引和保留了更多的131I-hVEGFsiRNA/SilenceMag。在有电磁场的情况下，131I-hVEGFsiRNA/SilenceMag治疗的肿瘤生长速度比没有电磁场的组和对照组慢近50%。免疫组织化学分析证实，在电磁场的引导下，131I-hVEGFsiRNA/SilenceMag靶向的肿瘤组织中的血管内皮生长因子蛋白水平低于未经电磁场照射的肿瘤组织和对照组。
结论
EMF引导的131I-hVEGFsiRNA/SilenceMag具有抗肿瘤作用。131I-hVEGFsiRNA/SilenceMag的协同治疗具有肿瘤治疗和成像的双重功能，有望成为一种很有前途的抗肝癌治疗方法。
Background
Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF).
Methods
hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment.
Results
131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control.
Conclusions
EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
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