实用医学杂志 ›› 2021, Vol. 37 ›› Issue (11): 1392-1396.doi: 10.3969/j.issn.1006⁃5725.2021.11.004

• 基础研究 • 上一篇    下一篇

白蛋白索拉非尼纳米粒的制备与 体外抗肝肿瘤活性评价

高文慧, 吴锦俊, 简晓顺, 贾小婷, 李靖   

  1. 广州医科大学附属肿瘤医院1 药学部,4 泌尿外科(广州 510095);2 广州中医药大学国际中医药转化医学研 究所(广州 510006);3 广州医科大学肿瘤研究所(广州 510095)

  • 出版日期:2021-06-10 发布日期:2021-06-10
  • 通讯作者: 李靖 E⁃mail:lijinggyzlyy@163.com
  • 基金资助:

    广东省自然科学基金(编号:2017A03031046);广州市恶性肿瘤治疗转化医学重点实验室建设项目(编号:2014SY000014)

Preparation of sorafenib loaded human serum albumin nanoparticles and evaluation of their anti ⁃hepatic tumor activity in vitro

GAO Wenhui,WU Jinjun,JIAN Xiaoshun,JIA Xiaoting,LI Jing.    

  1. Department of Phar⁃ macy,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangzhou 510095,China 

  • Online:2021-06-10 Published:2021-06-10
  • Contact: LI Jing E⁃mail:lijinggyzlyy@163.com

摘要:

目的 制备人血白蛋白包被的索拉非尼纳米粒(HSA⁃SRF⁃NPs),并评价其体外抗肝肿瘤活性。方法 化学交联法制备HSA⁃SRF⁃NPs,采用粒度分析仪和透射电镜对其进行表征,并计算载药量和包封率。荧光显微镜观察纳米粒在 BEL⁃7402 肝癌细胞内的蓄积,IncuCyte ZOOM 系统评价纳米粒对 BEL⁃ 7402 细胞的增殖抑制作用,流式细胞技术和 Western blotting 法考察 HSA⁃SRF⁃NPs BEL⁃7402 细胞的促凋 亡能力。结果 HSA⁃SRF⁃NPs 的水合粒径为(75.8 ± 2.6)nm,Zeta 电位为⁃(19.00 ± 1.02)mV,载药量和包 封率分别为(4.23 ± 0.03)%和(92.52 ± 2.40)%,能在 BEL⁃7402 细胞内蓄积,对 BEL⁃7402 细胞的增殖抑制作 用和促凋亡作用显著优于索拉非尼。结论 HSA⁃SRF⁃NPs 制剂性质良好,能显著提高索拉非尼的抗肝肿瘤活性,具有潜在的临床应用前景。

关键词:

Abstract:

Objective Human serum albumin ⁃ sorafenib nanoparticles(HSA ⁃ SRF ⁃NPs)were prepared and then their anti⁃hepatic tumor activity was evaluated in vitro. Methods HSA⁃SRF⁃NPs were prepared by chem⁃ ical cross⁃linking method,and their characterization was studied by a laser granulometer and a transmission elec⁃ tron microscope. The drug loading volume and encapsulation rate were calculated. Accumulation of nanoparticles in BEL ⁃ 7402 cells was observed by a fluorescence microscope,the proliferation inhibition of BEL ⁃ 7402 cells by nanoparticles was evaluated by the IncuCyte ZOOM system,and the proapoptotic effect of HSA⁃SRF⁃NPs on BEL⁃ 7402 cells was detected by flow cytometry and Western blotting. Results The particle size of HSA⁃SRF⁃NPs was (75.8 ± 2.6)nm and the Zeta potential was(-19.00 ± 1.02)mV,and the drug loading volume and encapsulation rate were(4.23 ± 0.03)% and(92.52 ± 2.40)% ,respectively. HSA ⁃ SRF ⁃ NPs could accumulate in BEL ⁃ 7402 cells,the proliferation inhibition and proapoptotic effect of HSA⁃SRF⁃NPs were significantly stronger than those of sorafenib. Conclusions HSA⁃SRF⁃NPs possess better properties,which can significantly improve the anti⁃hepatic tumor activity of sorafenib. They have potential prospect of clinical applications. 

Key words:

sorafenib, human serum albumin, nanoparticles, liver cancer