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大黄素纳米载药系统逆转人胆囊癌细胞上皮-间充质转化的可行性研究

Emodin nano drug delivery system reversing epithelial-mesenchymal transition of human gallbladder cancer cells

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【作者】 达选博张诚项雨凯胡海何川崎孔祥余邱晨吕贝宁张红雷王玉彬杨玉龙

【Author】 DA Xuanbo;ZHANG Cheng;XIANG Yukai;HU Hai;HE Chuanqi;KONG Xiangyu;QIU Chen;LYU Beining;ZHANG Honglei;WANG Yubin;YANG Yulong;Center of Gallbladder Disease,Shanghai East Hospital, School of Medicine, Tongji University;

【通讯作者】 杨玉龙;

【机构】 同济大学附属东方医院胆石中心

【摘要】 目的 为改善大黄素(EMO)水溶性差等问题,使用中空介孔硅纳米颗粒(HMSNs)包封EMO,体外培养人胆囊癌细胞(NOZ)评价其逆转胆囊癌细胞上皮-间充质转化(EMT)的效用。方法 通过油水双相反应结合模板法合成了具有介孔结构的中空介孔硅。利用物理吸附法制备负载EMO的纳米载药系统(EMO-HMSNs)。同时,采用扫描电镜(SEM)、透射电镜(TEM)观察纳米微粒形态,动态光散射(DLS)测定其电势和粒径大小,紫外分光光度计定量其载药率、包封率。体外实验中,我们用Western blotting、荧光显微镜、Transwell迁移实验分析EMO-HMSNs对胆囊癌细胞EMT的逆转效用。结果 SEM观察可见制备出的HMSNs微粒为球形且粒径均一,TEM观察可见HMSNs具有中空结构,DLS结果显示粒径约为201 nm,表面电位约为27.29 mV。荧光显微镜发现随着时间延长载药微粒在NOZ中聚集增加。NOZ中加入EMO-HMSNs共培养后,Transwell迁移实验发现其迁移能力被显著抑制(P<0.05),Western blotting结果表明E-cadherin、N-cadherin、Vimentin三种EMT相关蛋白表达量显著下降(P<0.05)。结论 EMOHMSNs具有良好的生物安全性,可以有效抑制胆囊癌细胞迁移。

【Abstract】 Objective To evaluate the effect of emodin-loaded hollow mesoporous silica nanoparticles(EMO-HMSNs) on epithelial-mesenchymal transition(EMT) of gallbladder carcinoma cells. Methods Hollow mesoporous silica with mesoporous structure was synthesized by oil-water two-phase reaction combined with template method. The EMO-HMSNs were prepared by physical adsorption. The morphology of nanoparticles was observed by scanning electron microscopy(SEM) and transmission electron microscopy(TEM). The potential and particle size were measured by dynamic light scattering(DLS). The drug loading rate and encapsulation efficiency were quantified by UV-VIS. The effect of EMO-HMSNs on EMT of gallbladder cancer cells was analyzed by Western blotting, fluorescence microscopy and transwell migration assay in vitro. Results SEM observation showed that the prepared hollow mesoporous silica nanoparticles(HMSNs) were spherical and uniform in size. TEM observation showed that HMSNs had a hollow structure. DLS results showed that the particle size was about 201 nm and surface potential was 27.29 mV. Laser confocal microscopy revealed that the accumulation of drug-loaded particles in gallbladder carcinoma cells increased over time. After co-cultured with EMO-HMSNs in gallbladder cancer cells, transwell migration assay showed that its migration ability was significantly inhibited(P<0.05), and Western blotting results showed that the expression of EMT-related proteins were significantly decreased(P<0.05). Conclusion EMO-HMSNs have good biosafety and can effectively inhibit the migration of gallbladder cancer cells.

【基金】 和记黄埔研究基金项目(CCP20060003P);浦东新区临床特色学科基金项目(PWYts2021-06)
  • 【文献出处】 肝胆胰外科杂志 ,Journal of Hepatopancreatobiliary Surgery , 编辑部邮箱 ,2023年05期
  • 【分类号】R735.8
  • 【下载频次】11
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