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配体密度对CdSe/ZnS量子点光谱、物理及生物学特性的影响。

Effect of ligand density on the spectral, physical, and biological characteristics of CdSe/ZnS quantum dots.

作者信息

Clarke Samuel J, Hollmann C A, Aldaye Faisal A, Nadeau Jay L

机构信息

Department of Biomedical Engineering, McGill University, Montreal, QC Canada H3A 2B4.

出版信息

Bioconjug Chem. 2008 Feb;19(2):562-8. doi: 10.1021/bc700404v. Epub 2008 Jan 18.

Abstract

Chemical modification of the surface of CdSe/ZnS quantum dots (QDs) with small molecules or functional ligands often alters the characteristics of these particles. For instance, dopamine conjugation quenches the fluorescence of the QDs, which is a property that can be exploited for sensing applications if the conjugates are taken up into living cells. However, different sizes and/or preparations of mercaptocarboxylic acid solubilized QDs show very different properties when incubated with cells. It is unknown what physical parameters determine a QDs ability to interact with a cell surface, be endocytosed, escape from endosomes, and/or enter the nucleus. In this study, we examine the surface chemistry of QD-dopamine conjugates and present an optimized method for tracking the attachment of small biomolecules to the surface. It is found that the fluorescence intensity, surface charge, colloidal stability, and biological interactions of the QDs vary as a function of the density of dopamine on the surface. Successful targeting of QD-dopamine to dopamine receptor positive PC12 cells correlates with greater homogeneity of particle thiol layer, and a minimum number of ligands required for specific association can be estimated. These results will enable users to develop methods for screening QD conjugates for biological activity before proceeding to experiments with cell lines and animals.

摘要

用小分子或功能性配体对CdSe/ZnS量子点(QDs)表面进行化学修饰,常常会改变这些颗粒的特性。例如,多巴胺共轭会淬灭量子点的荧光,如果共轭物被活细胞摄取,这一特性可用于传感应用。然而,巯基羧酸溶解的量子点在不同尺寸和/或制备条件下,与细胞孵育时表现出非常不同的特性。尚不清楚哪些物理参数决定了量子点与细胞表面相互作用、被内吞、从内体逃逸和/或进入细胞核的能力。在本研究中,我们研究了量子点-多巴胺共轭物的表面化学,并提出了一种优化方法来追踪小生物分子在表面的附着情况。研究发现,量子点的荧光强度、表面电荷、胶体稳定性和生物相互作用会随着表面多巴胺密度的变化而变化。量子点-多巴胺成功靶向多巴胺受体阳性的PC12细胞,与颗粒硫醇层更高的均匀性相关,并且可以估计特异性结合所需的最少配体数量。这些结果将使使用者能够开发在进行细胞系和动物实验之前筛选具有生物活性的量子点共轭物的方法。

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