乳糖基脂质磷酸钙基纳米颗粒:向肝细胞高效递送 DNA 的有效方法。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Masoomeh Khalifeh, Ali Badiee, Navid Ramezanian, Amirhossein Sahebkar, Atena Farahpour, Reza Kazemi Oskuee
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引用次数: 0

摘要

目的:为实现安全有效的基因治疗,将治疗核酸递送至靶点的能力至关重要。本研究开发了乳糖化磷酸脂质钙纳米颗粒(lac-LCP),用于向肝细胞靶向递送 pDNA。lac-LCP配方中含有乳糖改性胆固醇(CHL)和聚乙烯亚胺(PEI),乳糖改性胆固醇是一种能与肝细胞上表达的asialoglycoprotein受体(ASGR)结合的配体:傅立叶变换红外光谱(FT-IR)和核磁共振(NMR)用于监测化学修饰,动态光散射(DLS)和透射电子显微镜(TEM)用于研究 NPs 的理化性质。为了评估转染效率,使用荧光显微镜和流式细胞术评估了细胞摄取和 GFP 表达:结果表明,乳糖靶向颗粒(lac-LCP)对肝细胞的摄取显著增加。在 LCP 核心中加入 PEI/pDNA 比率为 1 的低分子量 PEI(1.8 KDa),可诱导 GFP 蛋白的高度表达(5 倍和 6 倍),其效率明显高于 PEI 1.8 KDa 和 Lipofectamine:结论:本文描述的 LCP NPs 的成功功能化和核输送表明,它有望成为一种高效的肝细胞核输送载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lactosylated lipid calcium phosphate-based nanoparticles: A promising approach for efficient DNA delivery to hepatocytes.

Objectives: For safe and effective gene therapy, the ability to deliver the therapeutic nucleic acid to the target sites is crucial. In this study, lactosylated lipid phosphate calcium nanoparticles (lac-LCP) were developed for targeted delivery of pDNA to the hepatocyte cells. The lac-LCP formulation contained lactose-modified cholesterol (CHL), a ligand that binds to the asialoglycoprotein receptor (ASGR) expressed on hepatocytes, and polyethyleneimine (PEI) in the core.

Materials and methods: Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) were used to monitor the chemical modification, and the physicochemical properties of NPs were studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). To evaluate transfection efficiency, cellular uptake and GFP expression were assessed using fluorescence microscopy and flow cytometry.

Results: The results revealed that lactose-targeted particles (lac-LCP) had a significant increase in cellular uptake by hepatocytes. The inclusion of a low molecular weight PEI (1.8 KDa) with a low PEI/pDNA ratio of 1 in the core of LCP, elicited high degrees of GFP protein expression (by 5 and 6-fold), which exhibited significantly higher efficiency than PEI 1.8 KDa and Lipofectamine.

Conclusion: The successful functionalization and nuclear delivery of LCP NPs described here indicate its promise as an efficient delivery vector to hepatocyte nuclei.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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