药学学报, 2019, 54(1): 151-158
引用本文:
喻兆阳, 薛慧颖, 裘琳, 刘异, 李娟. 脂质-中空介孔硅联合递送盐酸多柔比星及miR-375治疗肝癌的研究[J]. 药学学报, 2019, 54(1): 151-158.
YU Zhao-yang, XUE Hui-ying, QIU Lin, LIU Yi, LI Juan. Delivery of miR-375 and doxorubicin hydrochloride by lipid bilayer coated hollow mesoporous silica nanoparticles for liver cancer therapy[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 151-158.

脂质-中空介孔硅联合递送盐酸多柔比星及miR-375治疗肝癌的研究
喻兆阳1,2, 薛慧颖1, 裘琳1, 刘异1, 李娟1
1. 华中科技大学同济医学院附属同济医院药学部, 湖北 武汉 430030;
2. 华中科技大学同济医学院药学院, 湖北 武汉 430030
摘要:
本文旨在构建一种全新的脂质-中空介孔硅纳米载体(lipid bilayer coated hollow mesoporous silica nanoparticles,LHMSN)以联合递送基因药物与化疗药物,从而增强抗肿瘤药物对肝癌细胞的抑制活性。以盐酸多柔比星(doxorubicin hydrochloride,DOX)为模型药物,改良StÖber法合成中空介孔硅空载体,利用脂质体融合原理,制备共载DOX和miR-375的脂质-中空介孔硅纳米载体(lipid bilayer coated mesoporous silica nanoparticles loaded with DOX and miR-375,LHMSN-DOX/miR-375),并对纳米粒的形态、粒径、表面电位、载药量和体外释放度进行表征。同时考察纳米载体在人肝癌细胞(HepG2)中的摄取效率并进一步考察其对细胞活性和细胞迁移侵袭的抑制作用。结果表明,LHMSN-DOX/miR-375核壳结构清晰,外层脂质膜完整,内部HMSN介孔结构有序,平均粒径为(262 ±13.4)nm,具有一定的pH响应性,且LHMSN可有效将DOX和miR-375同时携带入胞。LHMSN-DOX/miR-375可显著抑制肝癌细胞增殖、迁移和侵袭并促进细胞凋亡。
关键词:    多柔比星      miR-375      药物递送系统      中空介孔硅      纳米载体     
Delivery of miR-375 and doxorubicin hydrochloride by lipid bilayer coated hollow mesoporous silica nanoparticles for liver cancer therapy
YU Zhao-yang1,2, XUE Hui-ying1, QIU Lin1, LIU Yi1, LI Juan1
1. Department of Pharmacy, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China;
2. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract:
This study was designed to prepare a novel lipid bilayer coated hollow mesoporous silica nanocarrier for co-delivery of gene drugs and chemotherapeutic drugs to enhance the inhibitory activity of antitumor drugs in hepatoma cells. Hollow mesoporous silica was synthesized by modified StÖber method. Lipid-fusion principle was used to prepare lipid-hollow co-loaded doxorubicin (DOX) and miR-375 (LHMSN-DOX/miR-375). Meanwhile, the morphology, particle size, surface potential, drug loading and release were characterized in vitro. The inhibition of cell proliferation, cell migration and invasion was then evaluated. The results indicated that the core-shell structure of LHMSN-DOX/miR-375 was clear with an intact outer lipid membrane and an ordered internal HMSN mesoporous structure. The drug release amount was pH responsive while the drug was rapidly released under simulated intracellular acidic conditions relative to normal physiological environment. Compared with free DOX, LHMSN-DOX/miR-375 can deliver DOX and miR-375 to liver cancer cells and inhibit the proliferation, migration and invasion of cells more effectively.
Key words:    doxorubicin    miR-375    drug delivery system    hollow mesoporous silicon    nanocarrier   
收稿日期: 2018-08-16
DOI: 10.16438/j.0513-4870.2018-0747
基金项目: 湖北省卫生计生委科研项目(WJ2017M077).
通讯作者: 李娟,Tel:86-27-69378114,E-mail:lijuan@tjh.tjmu.edu.cn
Email: lijuan@tjh.tjmu.edu.cn
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