介孔硅脂质囊纳米粒的研制及其细胞摄取机制研究

发布时间：2018-04-22 00:22

本文选题：介孔硅纳米粒 + 脂质膜囊　；参考：《中国医药工业杂志》2017年08期

【摘要】：采用改良Stober法一步合成氨基修饰的阳离子型介孔硅纳米粒(CMSN),结合薄膜水化法和高速离心法制备介孔硅脂质囊纳米粒(LP-CMSN)。所得LP-CMSN呈圆整球形、粒径分布均一、无团聚、具有明显的核-壳结构,粒径为(114.5±3.7)nm,ζ电位为(9.3±2.5)mV,多分散系数(PDI)为0.17±0.05。细胞水平上,LP-CMSN在0~100μg/ml范围内对Hela和A549细胞均无明显细胞毒性。以LP-CMSN为载体,选择多柔比星为模型药,采用饱和溶液吸附法制得了载药量为(15.58±3.25)%的载药纳米粒,有效改善了CMSN中药物易突释缺点。选择异硫氰酸荧光素(FITC)为荧光探针,合成了标记率为0.52%的荧光纳米粒。通过流式细胞仪和激光共聚焦显微镜考察LP-CMSN在Hela细胞的摄取机制和入胞途径。结果显示,CMSN通过网格蛋白介导的内吞途径摄取进入细胞,而LP-CMSN主要经过膜融合途径进入细胞,最终经溶酶体逃逸后释放药物发挥药效。因此,LP-CMSN具有良好的生物相容性和缓控释特性,并能通过无损害的膜融合途径摄取进入细胞,有望成为新型纳米递药载体。
[Abstract]:Modified Stober method was used to synthesize cationic mesoporous silicon nanocrystalline CMSNs modified with amino group. LP-CMSNs were prepared by membrane hydration and high speed centrifugation. The obtained LP-CMSN is spherical in shape, uniform in particle size distribution and no agglomeration, and has an obvious core-shell structure, with a particle size of 114.5 卤3.7 nm, a Zeta potential of 9.3 卤2.5mV and a polydispersity coefficient of 0.17 卤0.05. No cytotoxicity of LP-CMSN to Hela and A549 cells was observed in the range of 0 ~ 100 渭 g/ml. With LP-CMSN as carrier, doxorubicin as model drug and saturated solution adsorption method were used to obtain drug-loaded nanoparticles with a drug load of 15.58 卤3.25%, which effectively improved the weakness of drug sudden release in CMSN. Fluorescein isothiocyanate (FITC) was used as a fluorescent probe to synthesize fluorescent nanoparticles with a labeling rate of 0.52%. The uptake mechanism and entry pathway of LP-CMSN in Hela cells were investigated by flow cytometry and confocal laser microscopy. The results showed that CMSN was absorbed into cells through the endocytosis pathway mediated by griddle protein, while LP-CMSN entered the cells mainly through membrane fusion pathway, and finally released drugs through lysosome to play a drug effect. Therefore, LP-CMSN has good biocompatibility and slow controlled release characteristics, and can be absorbed into cells through a non-damaging membrane fusion pathway, which is expected to become a new type of nano-delivery drug carrier.
【作者单位】：杭州市萧山区第一人民医院;浙江大学医学院附属第二医院药剂科;
【基金】：浙江省中医药科技计划项目(2016ZA130) 杭州市卫生科技计划项目(2014B21) 杭州市科技发展计划项目(20163501Y70)
【分类号】：R943

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