Preparation of endostatin-loaded chitosan nanoparticles and antitumor effect of the nanoparticles combined with cisplatin in Lewis lung cancer mice

Ruilin Ding; Fang Xie; Yue Hu; Wenfeng He; Yu He; Qinglian Wen

doi:10.16016/j.1000-5404.201608148

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Preparation of endostatin-loaded chitosan nanoparticles and antitumor effect of the nanoparticles combined with cisplatin in Lewis lung cancer mice

Basic Medicin | 更新时间：2020-08-05

- Preparation of endostatin-loaded chitosan nanoparticles and antitumor effect of the nanoparticles combined with cisplatin in Lewis lung cancer mice
- J Third Mil Med Univ Vol. 39, Issue 2, Pages: 116-122(2017)
- 作者机构：
  
  646000 四川泸州, 西南医科大学附属医院肿瘤科
- 作者简介：
- 基金信息：
  
  Supported by the Special Project of Science and Technology Department of Sichuan Province(2014-10-146)
- DOI：10.16016/j.1000-5404.201608148
  CLC： R734.2;R943;R979.1
- Published：30 January 2017，
  
  Received：25 August 2016，
  
  Accepted：30 October 2016
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Ruilin Ding, Fang Xie, Yue Hu, et al. Preparation of endostatin-loaded chitosan nanoparticles and antitumor effect of the nanoparticles combined with cisplatin in Lewis lung cancer mice. [J]. J Third Mil Med Univ 39(2):116-122(2017)
DOI：

Ruilin Ding, Fang Xie, Yue Hu, et al. Preparation of endostatin-loaded chitosan nanoparticles and antitumor effect of the nanoparticles combined with cisplatin in Lewis lung cancer mice. [J]. J Third Mil Med Univ 39(2):116-122(2017) DOI： 10.16016/j.1000-5404.201608148.

摘要

目的

制备载内皮抑素(endostain，ES)壳聚糖纳米粒(endostatin-loaded chitosan nanoparticles，ES-NPs)，并探讨其联合顺铂(cisplatin，DDP)对小鼠Lewis肺癌模型的治疗作用。

方法

采用离子凝胶法制备ES-NPs，并对其形态及基本性质进行研究。建立小鼠Lewis肺癌皮下移植瘤模型，按随机数字表法分为对照组、ES组、DDP组、ES-NPs组、ES+DDP组、ES-NPs+DDP组。各组给药后，动态测量小鼠移植瘤体积，免疫组化检测移植瘤组织中微血管密度(microvessel density，MVD)，ELISA检测小鼠血清中内皮抑素和VEGF水平。

结果

制备的ES-NPs具有合适的粒径和较高的包封率，在体外具有明显缓释性，7 d累积释放量达(60.22±2.58)%。当ES-NPs与DDP联合时，能明显抑制肺癌移植瘤生长，观察结束时，ES-NPs+DDP组的抑瘤率为76.47%，明显高于ES+DDP组及其余各组(

＜0.05)。同时，免疫组化和ELISA检测结果证实了ES-NPs与DDP联合对肿瘤血管具有较强的抑制作用。

结论

内皮抑素纳米粒联用DDP可增强对小鼠Lewis肺癌移植瘤的抗瘤效果。

Abstract

Objective

To prepare endostatin-loaded chitosan nanoparticles (ES-NPs)

and investigate the antitumor effect of the nanoparticles combined with cisplatin (DDP) in Lewis Lung cancer mice.

Methods

ES-NPs were prepared with a simple ionic crosslinking method. The characterization of ES-NPs

including size distribution

zeta potential

loading efficiency

encapsulation efficiency and release behavior

was determined. Subcutaneous Lewis lung cancer xenograft model of C57BL/6J mice was established

and the mice were randomly divided into 6 groups: control group (0.9% NaCl)

ES group

DDP group

ES-NPs group

ES+DDP group

and ES-NPs+DDP group. After drug administration

the volume of xenograft tumor in different groups was measured dynamically. The microvascular density (MVD) in xenograft tumor tissues was detected by immunohistochemical assay. The serum vascular endothelial growth factor (VEGF) and endostatin levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results

ES-NPs were successfully synthesized and had suitable size distribution and high encapsulation efficiency. The NPs were spherical and homogeneous in shape

and exhibited an ideal releasing profile

in vitro

. The tumor growth was significantly inhibited after treatment with ES-NPs combined with DDP. The tumor inhibitory rate was much higher in the ES-NPs+DDP group than in the other groups (

＜0.05). Moreover

the results of immunohistochemical assay and ELISA confirmed that ES-NPs combined with DDP had strong effect on inhibiting tumor angiogenesis.

Conclusion

ES-NPs can overcome the shortcomings of free ES

such as short retention time in circulation

and can enhance antitumor efficacy of ES. When the nanoparticles are combined with DDP

the antitumor effect becomes stronger.

关键词

肺肿瘤内皮抑素纳米粒壳聚糖顺铂

Keywords

lung cancerendostatinnanoparticleschitosancisplatin

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