载盐酸伊立替康的半乳糖修饰脂质-介孔硅核壳纳米粒对肝癌细胞的抑制效果  

Antitumor efficacy of irinotecan-loaded galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles against hepatocellular carcinoma cells

作　　者：陈熙[1,2] 张馨欣[2] 李菲菲[2] 赵亚男[1,2] 贾征[3] 甘勇[2] 李娟[1] 

机构地区：[1]中国药科大学,江苏南京210009 [2]中国科学院上海药物研究所,上海201203 [3]唐山职业技术学院,河北唐山063004

出　　处：《药学学报》2014年第5期718-725,共8页Acta Pharmaceutica Sinica

基　　金：河北省自然科学基金资助项目(C2011319010);"十二五"重大专项创制项目(2009ZX09310-004)

摘　　要：本文旨在构建一种全新的半乳糖修饰的脂质-介孔硅核壳纳米载体(galactosyl modified lipid bilayercoated mesoporous silica nanoparticles,GPEM)以增强抗肿瘤药物对肝癌细胞的抑制效果。研究以盐酸伊立替康(irinotecan,CPT-11)为模型药物,修饰半乳糖配基的Pluronic P123(Gal-P123)和磷脂材料构建功能性脂质膜,结合介孔硅纳米粒(mesoporous silica nanoparticles,MSNs),采用薄膜分散法制备GPEM,表征其粒径、电位、微观形态和体外释放行为。研究纳米载体在人肝癌细胞Huh-7细胞摄取能力、胞内抗肿瘤药物蓄积水平,并以细胞凋亡率和细胞活性评价其抗肿瘤细胞效果。结果表明:GPEM核壳结构清晰,外层脂质膜完整,内部MSNs介孔结构有序;平均粒径为(78.01±2.04)nm。功能性脂质膜在正常生理环境下可防止药物提前泄露;在胞内酸性条件下脂膜破裂,药物快速释放。同时,功能性脂质膜可有效提高载体与Huh-7细胞的亲和性,增加细胞摄取。与MSNs相比,GPEM使胞内CPT-11蓄积浓度提高约4倍,半数抑制浓度(IC50)降低了约2倍,细胞凋亡率上升了48.6%,抗肝癌细胞效果显著增强。The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles （GPEM） to enhance the antitumor efficacy against hepatocellular carcinoma ceils. The irinotecan （CPT-11） loaded mesoporous silica nanoparticles （MSNs） was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of （78.01±2.04） nm. The low leakage rate in normal ohvsiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration （IC50） values of CPT- 11 by 2 times, indicating stronger cell cytotoxicity.

关 键 词：介孔硅 肝癌 半乳糖 纳米粒 盐酸伊立替康 

分 类 号：R943[医药卫生—药剂学]