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中华腔镜泌尿外科杂志(电子版) ›› 2019, Vol. 13 ›› Issue (04) : 221 -224. doi: 10.3877/cma.j.issn.1674-3253.2019.04.002

所属专题: 文献

实验研究

基于苯丙氨酸的聚酯酰胺纳米递药系统制备及其体外抗前列腺癌的研究
张俊夫1, 熊海云2, 段剑礼1, 李璐婧2, 康洋2, 庞俊2,()   
  1. 1. 510630 广州,中山大学附属第三医院泌尿外科
    2. 518107 深圳,中山大学附属第七医院泌尿外科
  • 收稿日期:2019-04-15 出版日期:2019-08-01
  • 通信作者: 庞俊
  • 基金资助:
    国家自然科学基金面上项目(81772754); 广东省自然科学基金重大基础研究培育项目(2017A030308009)

Construction and in vitro antitumor effect on prostate cancer of phenylalanine-based poly(ester amide)snanoparticles drug delivery system

Junfu Zhang1, Haiyun Xiong2, Jianli Duan1, Lujing Li2, Yang Kang2, Jun Pang2,()   

  1. 1. Department of Urology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
    2. Department of Urology, the Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
  • Received:2019-04-15 Published:2019-08-01
  • Corresponding author: Jun Pang
  • About author:
    Corresponding author: Pang Jun, Email:
引用本文:

张俊夫, 熊海云, 段剑礼, 李璐婧, 康洋, 庞俊. 基于苯丙氨酸的聚酯酰胺纳米递药系统制备及其体外抗前列腺癌的研究[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2019, 13(04): 221-224.

Junfu Zhang, Haiyun Xiong, Jianli Duan, Lujing Li, Yang Kang, Jun Pang. Construction and in vitro antitumor effect on prostate cancer of phenylalanine-based poly(ester amide)snanoparticles drug delivery system[J/OL]. Chinese Journal of Endourology(Electronic Edition), 2019, 13(04): 221-224.

目的

探究基于苯丙氨酸的聚酯酰胺的纳米递药系统的制备及其对体外培养前列腺癌细胞的抑制效果。

方法

采用纳米沉淀法制备聚酯酰胺纳米粒,利用透射电镜和纳米电位仪测量纳米粒的形貌和大小分布,利用破碎沉淀法与荧光磷光光谱仪测定其载药量和包封率。采用四甲基偶氮唑盐微量酶反应比色法测定载药纳米粒对前列腺癌细胞LNCaP的抑制效果,采用膜联蛋白V-APC/7AAD双染法并用流式细胞仪测定其对肿瘤细胞的凋亡诱导作用。

结果

采用纳米沉淀法成功制备了空白及包载多柔吡星(DOX)的载药聚酯酰胺纳米粒,粒径约为90~110 nm,大小分布较为均匀。空白纳米粒在不同浓度下均显示出良好的生物相容性,高浓度100 μg/ml的材料作用下,LNCaP的细胞活力仍保持在(95.32±3.97)%。与DOX组的IC50 (3.29±0.63)μg/ml相比,载药纳米粒对前列腺癌细胞活性抑制明显,IC50为(1.21±0.43)μg/ml,差异具有统计学意义(t=6.693,P<0.001)。流式细胞仪检测载药纳米粒能有效诱导前列腺癌细胞进入中晚期凋亡,对照组、DOX组与DOX@8p6组凋亡率分别为2.32%、29.16%和61.62%,后两组间差异具有统计学意义(χ2=2217,P<0.001),且DOX@8p6组凋亡情况多于DOX组(t=11.238,P<0.001),显示出载药纳米粒对前列腺癌细胞LNCaP更高的促凋亡效率。

结论

基于苯丙氨酸的聚酯酰胺纳米粒具有良好的生物相容性,其作为递送抗肿瘤药物多柔吡星的纳米药物载体时能有效地直接抑制前列腺癌肿瘤细胞活性及诱导肿瘤细胞凋亡。

Objective

To study the construction of phenylalanine-based poly(ester amide)sas drug delivery system and its inhibition of in vitro prostate cancer cell LNCaP.

Methods

The phenylalanine-based poly(ester amide)s nanoparticles were synthesized by nanoprecipitation. The morphology and size distribution of nanoparticle were inspected by transmission electron microscopy and nanoparticle size analyzer. Drug loading and encapsulation rate were measured using fragmentation precipitation method by fluorescent phosphorescence spectrometer. Inhibition of prostate cancer cell LNCaP using doxorubicin-loaded phenylalanine-based poly(ester amide)s nanoparticle were inspected by MTT method and cell apoptosis effect was analyzed by V-APC/7AAD double staining method.

Results

The phenylalanine-based poly(ester amide)s nanoparticles were synthesized successfully as doxorubicin delivery system with a uniform size of about 90-110 nm. The blank nanoparticles showed a great biocompatibility at different concentrations. The cell viability of LNCaP remained at (95.32±3.97)% at a high blank nanoparticle concentration of 100 μg/ml. Compared with the DOX group whose IC50 was (3.29±0.63) μg/ml, the activity of prostate cancer cells co-cultured with drug-loaded nanoparticles was significantly inhibited, whose IC50 was (1.21±0.43) μg/ml, which was statistically different (t= 6.693, P<0.001). The cell apoptosis effectively induced by drug-loaded nanoparticles was measured by flow cytometry detection. The control group, DOX group and DOX@8p6 group were 2.32%, 29.16% and 61.62%, respectively, while the difference between the three groups was statistically significant (F=294.44, P<0.001), and the DOX@8p6 group had more apoptosis than the DOX group (t=11.238, P<0.001), showing drug-loaded nanoparticles had higher pro-apoptotic efficiency against prostate cancer cell line LNCaP.

Conclusion

It demonstrated that the biocompatible phenylalanine-based poly(ester amide)s nanoparticles as doxorubicin delivery system could provide effective prostate cancer cell inhibition and high cell apoptosis.

表1 空白及载药8p6纳米粒表征分析
图1 MTT法测定载药纳米粒对肿瘤细胞抑制作用
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