mRNA脂质纳米粒载药系统的构建及体外评价
投稿时间:2023-02-16  修订日期:2023-03-15  点此下载全文
引用本文:陈昕璐,高原,李鹃鹃,郭欢欢,王卓,高申.mRNA脂质纳米粒载药系统的构建及体外评价[J].药学实践杂志,2023,41(5):291~295
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陈昕璐 海军军医大学第一附属医院, 上海 200433  
高原 复旦大学药学院, 上海 200032  
李鹃鹃 海军军医大学第一附属医院, 上海 200433  
郭欢欢 海军军医大学第一附属医院, 上海 200433  
王卓 海军军医大学第一附属医院, 上海 200433  
高申 海军军医大学第一附属医院, 上海 200433 liullk@126.com 
基金项目:国家自然科学基金(81972392,81972891);上海市科学技术委员会基础研究项目(18JC1414200)
中文摘要:目的 构建脂质纳米粒DLin-LNP,以EGFP-mRNA为模型药,考察DLin-LNP对于mRNA的体外递送能力。方法 采用薄膜水化法制备DLin-LNP, 并进一步制备 DLin@mRNA,对纳米粒进行表征,使用激光扫描共聚焦显微镜观察脂质纳米粒胞内的分布情况,以RM-1细胞为模型考察胞内转染情况。结果 成功制备了脂质纳米粒DLin-LNP,其粒径为(151.1±2.1) nm,空载电位为(23.7±0.5) mV。DLin-LNP在RM-1细胞中转染mRNA效率较高,其毒性远低于市售脂质体Lipo8000且 DLin-LNP脂质纳米粒稳定性好。结论 DLin-LNP具有高转染效率和安全性,且稳定性好,可作为mRNA递送载体,为后续脂质纳米粒肿瘤治疗中的应用提供依据。
中文关键词:脂质纳米粒  DLin-MC3-DMA  信使核糖核酸  药物递送
 
Construction and in vitro evaluation of an LNP system for mRNA delivery
Abstract:Objective To construct lipid nanoparticles DLin-LNP for mRNA delivery. Methods DLin-LNP was prepared by thin film hydration method, and DLin-LNP/mRNA was further constructed by using EGFP-mRNA as model drug. The particle size, zeta potential, and appearance morphology were measured. Furthermore, the intracellular distribution and transfection of DLin-LNP/mRNA in RM-1 cells was investigated by laser scanning confocal microscope. Results DLin-LNP was successfully prepared. The average particle size was about (151.1±2.1) nm, the no-load potential was (23.7±0.5) mV. The cytotoxicity of DLin-LNP was far lower than that of the commercially available liposomal Lipo8000. The results of transfection experiment indicated that DLin-LNP has high transfection efficiency for mRNA delivery with low cytotoxicity and good stability. Conclusion DLin-LNP could become a potential mRNA vector for gene therapy.
keywords:LNP  DLin-MC3-DMA  mRNA  drug delivery
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