基础研究(Basic Research)

载阿帕替尼纳米胶束对脐静脉内皮细胞的抑制作用研究

Published at: 2017年第26卷第5期

王硕 1,2 , 李永盛 1,2 , 边睿 1,2 , 戴一星 3 , 郎美东 3 , 刘颖斌 1,2 , 施伟斌 1,2
1 上海交通大学医学院附属新华医院 普通外科,上海 200092
2 上海市胆道疾病研究所,上海 200092
3 华东理工大学材料学院,上海 200237
通讯作者 伟斌 施 Email: weibindr@aliyun.com
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2017.05.011
基金:
上海市科委纳米专项基金资助项目 11nm0503700
新华医院滚动基金资助项目 XHYYGD2015036

摘要

目的:探讨载阿帕替尼(apatinib)纳米胶束对脐静脉内皮细胞(HUVECs)的抑制作用及其释放规律与安全性。方法:分别用紫外-吸收法和溶血实验检测载apatinib纳米胶束的释放率与使用安全性,然后分别用CCK-8实验、迁移实验、体外小管形成实验观察载apatinib纳米胶束对HUVECs的抑制作用。结果:载apatinib纳米胶束有短暂的突释效应(2 h达20.5%),随后呈缓慢释放(72 h达62.9%),其溶血实验阴性。载apatinib纳米胶束与单纯apatinib均能明显抑制HUVECs的增殖,并呈浓度与时间依赖性(均P<0.05);48 h内载apatinib纳米胶束对HUVECs的抑制率小于单纯apatinib组(48 h IC50:1.385 µmol/L vs. 0.768 µmol/L,P=0.012),但随着时间延长至72 h,载apatinib纳米胶束的抑制率超过单纯apatinib(63.34% vs. 59.70%,P=0.005)。载apatinib纳米胶束与单纯apatinib均能明显抑制HUVECs的迁移及小管形成,并呈浓度与释放时间依赖性,且体外释放3 d的载apatinib纳米胶束对HUVECs迁移及成管的抑制超过单纯apatinib(均P<0.05)。结论:载apatinib纳米胶束具备良好的安全性及缓释性,对apatinib进行纳米包载可增强apatinib对HUVECs的抑制作用并延长apatinib的作用时间窗。


Inhibitory effect of apatinib-loaded nanomicelles on human umbilical vein endothelial cells

Abstract

Objective: To investigate the inhibitory effect of apatinib-loaded nanomicelles on human umbilical vein endothelial cells (HUVECs) as well as its release pattern and safety. Methods: The release rate and use safety of apatinib-loaded nanomicelles was determined by ultraviolet spectrophotometry method and hemolytic assay, respectively. And then, the inhibitory effect of apatinib-loaded nanomicelles on HUVECs was tested by CCK-8 assay, migration assay and tube formation assay, respectively. Results: The apatinib-loaded nanomicelles showed a transient immediate-release (2 h release rate reached 20.5%) and then a slow release (72 h release rate was 62.9%), and the results of hemolytic assay were negative. The proliferation of HUVECs was significantly inhibited by either apatinib-loaded nanomicelles or free apatinib in a concentration- and time-dependent manner (all P<0.05); the inhibition rate of apatinib-loaded nanomicelles on HUVECs was lower than those of free apatinib within 48 h (48 h IC50: 1.385 µmol/L vs. 0.768 µmol/L, P=0.012), but it surpassed that of free apatinib with time up to 72 h (63.34% vs. 59.70%, P=0.005). The migration and tube formation of HUVECs were significantly suppressed by both apatinib-loaded nanomicelles and free apatinib in a concentration- and releasing time-dependent manner, and the inhibitory effects of apatinib-loaded nanomicelles with 3-d release on migration and tube formation of HUVECs were significantly greater than those of free apatinib (both P<0.05). Conclusion: The apatinib-loaded nanomicelles have good safety and sustained release property. Nanoencapsulation can enhance the inhibitory effect of apatinib on HUVECs and extend its action time window.


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引用

引用本文: 硕 王, 永盛 李, 睿 边, 一星 戴, 美东 郎, 颖斌 刘, 伟斌 施. 载阿帕替尼纳米胶束对脐静脉内皮细胞的抑制作用研究 [J]. 中国普通外科杂志, 2017, 26(5): 597-606.
Cite this article as: WANG Shuo, LI Yongsheng, BIAN Rui, DAI Yixing, LANG Meidong, LIU Yingbin, SHI Weibin . Inhibitory effect of apatinib-loaded nanomicelles on human umbilical vein endothelial cells [J]. Chin J Gen Surg, 2017, 26(5): 597-606.