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一种新型荧光探针,可更有效地监测细胞内的纳米药物输送系统。

A novel fluorescent probe for more effective monitoring of nanosized drug delivery systems within the cells.

机构信息

University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.

出版信息

Int J Pharm. 2011 Sep 15;416(1):384-93. doi: 10.1016/j.ijpharm.2011.06.046. Epub 2011 Jul 1.

DOI:10.1016/j.ijpharm.2011.06.046
PMID:21745558
Abstract

To improve visualization of nanoparticles within the cells' compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DACA exhibits good biocompatibility, its solubility and emission spectrum are not sensitive to changes in pH value. Solid lipid nanoparticles (SLN) labeled with 14-DACA (SLN-D) and frequently used 6-coumarin (SLN-C) were utilized to evaluate probes' properties in the trafficking and intracellular localization of nanoparticles. SLN-D were seen as distinct blue dots in the cellular environment in contrast to SLN-C which were hardly to recognize due to the self-quenching of 6-coumarin, its leakage and distribution in intracellular compartments. Spectra of 14-DACA indicated the possibility of spectral resolution from both green and red fluorophores allowing clear multicolor imaging of organelles in both fixed and living cells. The results showed valuableness of new probe for trafficking of the drug nanocarriers intracellularly in a kinetic and sensitive manner. Such studies are of great importance in investigations aimed to clarify subcellular targeted drug delivery, controlled release and even to identify toxicological changes.

摘要

为了提高细胞隔室内纳米粒子的可视化程度,我们合成了一种基于香豆素的荧光衍生物,十四烷基二乙氨基香豆素酰胺,14-DACA。在该化合物中,香豆素发色团与十四烷基烷基链相连,这有助于该探针的亲脂性和轻微的两亲性。14-DACA 具有良好的生物相容性,其溶解度和发射光谱对 pH 值的变化不敏感。用 14-DACA(SLN-D)标记的固体脂质纳米颗粒(SLN)和常用的 6-香豆素(SLN-C)被用于评估探针在纳米颗粒的运输和细胞内定位中的性质。与 SLN-C 相比,SLN-D 在细胞环境中呈现出明显的蓝色斑点,因为 6-香豆素的自猝灭、其泄漏和在细胞内隔室中的分布使得 SLN-C 难以识别。14-DACA 的光谱表明有可能从绿色和红色荧光团中进行光谱分辨率,从而能够清晰地对固定和活细胞中的细胞器进行多色成像。结果表明,新探针对于以动态和敏感的方式在细胞内运输药物纳米载体具有重要价值。此类研究对于旨在阐明亚细胞靶向药物递送、控制释放甚至识别毒理学变化的研究非常重要。

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