木犀草素/阿霉素双载药纳米粒治疗三阴乳腺癌的体外研究  

Construction of the Luteolin/Doxorubicin Dual-drug Delivery Nanoparticals for Triple-negative Breast Cancer Treatment in Vitro

作　　者：常炳程 何蔚 夏志鸿 CHANG Bingcheng;HE Wei;XIA Zhihong(The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550003,China.)

机构地区：[1]贵州中医药大学第二附属医院,贵州贵阳550003

出　　处：《药品评价》2021年第20期1226-1229,共4页Drug Evaluation

基　　金：贵州省科技支撑计划,黔科合支撑([2020]4Y197);贵州省卫生计生委科学技术基金(gzwjkj2020-1-215)。

摘　　要：目的:制备纳米粒搭载难溶性天然抗肿瘤化合物木犀草素(luteolin,LUT)与化疗药阿霉素(doxorubicin,DOX),研究强效治疗三阴乳腺癌并抑制肿瘤转移效应。方法:采用聚乳酸-羟基乙酸共聚物[poly(lactic acid-glycolic acid),PLGA]单乳法形成纳米粒同时包封阿霉素与木犀草素,并利用电镜与动态光散射技术表征其基本特性;用不同缓冲溶液模拟肿瘤微环境并检验其体外药物释放性能;利用MTT细胞毒性实验检验其对三阴乳腺癌MDAMB-231的杀伤效果;Transwell细胞迁移与侵袭模型检验其对三阴乳腺癌的转移抑制效果。结果:成功构建双载药纳米粒PLGA-NPs@DOX/LUT,粒径(114.8±6.2)nm呈规则球形而且分散性良好;木犀草素载药量(10.15±0.17)%,阿霉素载药量(18.11±0.14)%,在微酸性环境中具备药物缓释能力;体外细胞实验中对三阴乳腺癌细胞具有强效杀伤效果,而且能够有效抑制其癌细胞转移效应。结论:成功制备能够递送木犀草素/阿霉素的双载药纳米粒,其具有治疗三阴乳腺癌并抑制其转移的潜在价值。Objective:To deliver the natural insoluble antitumor compound,prepare nanoparticles which co-loaded the Luteolin with Doxorubicin for enhanced chemotherapy to avoid triple-negative breast cancer(TNBC)metastasis.Methods:Luteolin/Doxorubicin loaded by poly(lactic acid-glycolic acid)(PLGA)nanoparticals were composed through single emulsion method,then characterized by electron microscopes and dynamic light scattering.In vitro drug release profile were detected in different pH buffer solution to mimic the physiological or tumor microenvironment.The TNBC cell killing ability of nanoparticals was assessed by MTT assay on MDA-MB-231.Transwell migration and invasion assay were also performed to evaluate the metastasis reversing ability.Results:Monodisperse spherical Luteolin/Doxorubicin loaded PLGA nanoparticals(PLGA-NPs@DOX/LUT)were successfully prepared with the mean size of(114.8±6.2)nm,which contained(18.11±0.14)%mess for Doxorubicin and(10.15±0.17)%for Luteolin.In vitro,PLGA-NPs@DOX/LUT possessed the sustained drug released ability in acidic microenvironment and enhanced cancer cell killing effect.Further,PLGA-NPs@DOX/LUT significantly reversed the TNBC migration and invasion effect in Transwell assay.Conclusion:Luteolin/Doxorubicin dual-drug loaded nanoparticals were successfully fabricated for enhanced TNBC treatment,which might be a promising candidate for reversing cancermetastasis.

关 键 词：三阴乳腺癌 纳米粒 药物载体 木犀草素 体外研究 

分 类 号：R737.9[医药卫生—肿瘤]