Therapeutic Effect of Sorafenib-Loaded TPGS-b-PCL Nanoparticles on Liver Cancer.
Therapeutic Effect of Sorafenib-Loaded TPGS-b-PCL Nanoparticles on Liver Cancer.
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DOI：
10.1166/jbn.2018.2529
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发表时间：
2018-02
影响因子：
2.9
通讯作者：
Xiaolong Tang;Yanguan Lyu;Da Xie;Amin Li;Yong Liang;Donghui Zheng
中科院分区：
文献类型：
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作者：
Xiaolong Tang;Yanguan Lyu;Da Xie;Amin Li;Yong Liang;Donghui Zheng
索拉非尼对肝细胞癌（HCC）显示出适度的治疗效果，但需要更有效的治疗方法。本研究的目的是测试使用载有索拉非尼的聚合物纳米颗粒（NP-SFB）来增强对肿瘤的有效性的可行性。采用改良的纳米沉淀法制备了可生物降解的d-α-生育酚聚乙二醇1000琥珀酸酯聚己内酯（TPGS-b-PCL）纳米粒，并在HepG 2肝癌细胞和肝癌小鼠移植瘤模型上进行了抗肿瘤作用的实验研究。SFB载TPGS-b-PCL纳米粒具有合适的形状、平均粒径（122.3 nm）、粒径分布（用透射电子显微镜和动态光散射测定）、稳定性、药物释放速率和载药量，是一种有效的药物递送载体。与游离SFB相比，负载SFB的TPGS-b-PCL NPs更有效地抑制HepG 2细胞生长，用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑测定、蛋白质印迹和流式细胞术分析证实。与这些体外研究一致，NP-SFB也比游离SFB更有效地延迟HCC异种移植模型中的肿瘤生长（27天对20天; P < 0.05）。未观察到NP-SFB治疗的不良反应。因此，负载SFB的TPGS-b-PCL纳米颗粒表现出抗肝癌活性和安全性，这可能使它们成为肝癌治疗试验的候选者。
Sorafenib has shown modest therapeutic effectiveness against hepatocellular carcinoma (HCC), but more effective therapies are needed. The objective of this research was to test the feasibility of using sorafenib-loaded polymer nanoparticles (NP-SFB) to enhance effectiveness against the tumor. Biodegradable d-α-tocopherol polyethylene glycol 1000 succinatepolycaprolactone (TPGS-b-PCL) nanoparticles were prepared by a modified nanoprecipitation method and tested for anti-tumor effect in HepG2 hepatoma cells and a HCC xenograft mouse model. The SFB-loaded TPGS-b-PCL nanoparticles had appropriate shape, mean particle size (122.3 nm), size distribution (determined with transmission electron microscopy and dynamic light scattering), stability, drug-release rate, and drug-loading content of an efficient drug-delivery vehicle. Compared with free SFB, the SFB-loaded TPGS-b-PCL NPs more effectively suppressed HepG2 cell growth, confirmed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, western blotting and flow cytometry analysis. Consistent with these in vitro studies, NP-SFB also more effectively delayed tumor growth in the HCC xenograft model than did free SFB (27 days vs. 20 days; P < 0.05). No adverse effect of NP-SFB treatment was observed. Therefore, the SFB-loaded TPGS-b-PCL NPs exhibited anti-HCC activity and safety that may make them candidates for trial in hepatoma therapy.