[1]唐　岩,李　渊,郑翠霞,等.酸敏感型自组装苯硼酸治疗系统的制备及体外抗肿瘤活性[J].新乡医学院学报,2019,36(7):605-611.[doi:10.7683/xxyxyxb.2019.07.002]
　TANG Yan,LI Yuan,ZHENG Cui-xia,et al.Construction of a acid-sensitive self-assembled phenylboronic acid-based therapy system and its antitumor effect in vitro[J].Journal of Xinxiang Medical University,2019,36(7):605-611.[doi:10.7683/xxyxyxb.2019.07.002]
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酸敏感型自组装苯硼酸治疗系统的制备及体外抗肿瘤活性
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年7
页码:
605-611
栏目:
基础研究
出版日期:
2019-07-05

文章信息/Info

Title:
Construction of a acid-sensitive self-assembled phenylboronic acid-based therapy system and its antitumor effect in vitro
作者:
唐　岩1; 李　渊1; 郑翠霞2; 王　蕾2; 丁　波1
（1.南阳市第一人民医院普外科，河南　南阳　473000；2.郑州大学药学院，河南　郑州　450001）
Author(s):
TANG Yan1; LI Yuan1; ZHENG Cui-xia2; WANG Lei2; DING Bo1
（1.Department of General Surgery，the First People′s Hospital of Nanyang City，Nanyang 473000，Henan Province,China;2.School of Pharmaceutical Sciences，Zhengzhou University，Zhengzhou 450001,Henan Province,China）
关键词:
苯硼酸; 多西紫杉醇; 酸敏感性; 抗肿瘤活性
Keywords:
phenylboronic acid; docetaxel; acid sensitivity; antitumor effect
分类号:
R914.2
DOI:
10.7683/xxyxyxb.2019.07.002
文献标志码:
A
摘要:
目的　构建基于苯硼酸酯的具有泊洛沙姆外壳和酸敏感性内核的自组装纳米肿瘤治疗系统，提高药物在肿瘤部位的蓄积能力，并探讨该治疗系统的体外抗肿瘤效果。方法　采用乳化溶剂挥发法制备多西紫杉醇（DTX）/苯硼酸酯纳米粒（PNPs）；以人肝癌HepG2细胞为细胞模型，将细胞分为空白对照组、PNPs组、DTX组、DTX/PNPs组。采用四甲基偶氮唑盐法检测各组细胞的抑制率，采用流式细胞术检测各组细胞周期分布，采用碘化丙啶（PI）染色法检测各组细胞凋亡情况。结果　苯硼酸能够对肿瘤部位的弱酸性环境产生快速的响应，具有酸敏感特性，在pH值为5.0、6.0、7.4的条件下，药物累计释放百分数分别为（80.61±3.09）%、(55.81±3.05)%、（11.88±1.90）%，pH值为5.0和6.0时的药物累积释放百分数高于pH值为7.4时（P<0.05）。药物作用48 h后，DTX浓度为0.135、0.270、0.800、2.500、5.000 mg·L-1时，DTX/PNPs（pH值为6.5）组、DTX/PNPs（pH值为7.4）组细胞抑制率高于DTX组（P<0.01）；DTX/PNPs（pH值为6.5）组细胞抑制率高于DTX/PNPs（pH值为7.4）组（P<0.01）。PNPs组G0/G1、S和G2/M期细胞所占百分比与空白对照组比较差异无统计学意义（P>0.05）；DTX、DTX/PNPs组G0/G1期细胞所占百分比显著低于空白对照组，S期细胞所占百分比显著高于空白对照组（P<0.01）。空白对照组与PNPs组细胞凋亡指数比较差异无统计学意义（P>0.05），DTX组、DTX/PNPs组细胞凋亡指数高于空白对照组（P<0.05）。结论　共价自组装DTX/PNPs不仅能够在受体介导的作用下增强进入细胞的能力，而且可以快速响应肿瘤细胞内的酸性环境，达到高效递送药物的目的，具有良好的pH敏感性和体外抗肿瘤效果。
Abstract:
Objective　To constructed a self-assembled nano-cancer therapy system with a poloxamer shell and a pH responsive inner core based on borosamic acid ester，in order to improve drug accumulation at tumor site and explore the antitumor effect in vitro.Methods　Docetaxel(DTX)/phenylboronic acid-based self-assembly nanoparticles(PNPs) were prepared by emulsification，and the human hepatocellular carcinoma cells HepG2 were divided into blank control group,PNPs group,DTX group and DTX/PNPs group.The cell inhibition rate of each group was detected by methyl thiazolyl tetrazolium method.The cell cycle in the each group was detected by flow cytometry assay.The cell apoptosis rate in each group was detected by propidium iodide staining.Results　Phenylboronic acid had a rapid response to the weakly acidic environment of the tumor site.The cumulative release rate of the drug at pH 5.0，pH 6.0 and pH 7.4 was (80.61±3.09)%,(55.81±3.05)% and （11.88±1.90）%.The cumulative drug release rate of the drug at pH 5.0 and pH 6.0 was higher than that at pH 7.4 (P<0.05);after 48 hours of drug action,the DTX concentration was 0.135,0.270,0.800,2.500,and 5.000 mg·L-1,the cell inhibition rates in the DTX/PNPs (pH 6.5) group and DTX/PNPs (pH 7.4) group were higher than those in the DTX group（P<0.01）.The cell inhibition rate in the DTX/PNPs (pH 6.5) group was higher than that in the DTX/PNPs (pH 7.4) group (P<0.01).There was no significant difference in the percentage of G0/G1,S and G2/M phase cells between the PNPs group and the blank control group (P>0.05).The percentage of G0/G1 phase cells in the DTX group and the DTX/PNPs group were significantly lower than those in the blank control group and the percentage of S phase cells was significantly higher than that in the blank control group (P<0.01).There was no significant difference in apoptotic index between the control group and the PNPs group (P>0.05);the apoptotic index in the DTX group and DTX/PNPs group was higher than that in the control group (P<0.05).Conclusion　Covalently self-assembled DTX/PNPs nanoparticles can not only enhance the ability to enter cells under the action of receptors,but also can quickly respond to the acidic environment in tumor cells.These can achieve the purpose of efficient drug delivery with good pH sensitivity and in vitro antitumor effect.

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更新日期/Last Update: 2019-07-05