Ulusoy Mehriban, Jonczyk Rebecca, Walter Johanna-Gabriela, Springer Sergej, Lavrentieva Antonina, Stahl Frank, Green Mark, Scheper Thomas
Department of Physics, King's College London , The Strand, WC2R 2LS London, U.K.
Bioconjug Chem. 2016 Feb 17;27(2):414-26. doi: 10.1021/acs.bioconjchem.5b00491. Epub 2015 Nov 20.
Ligands used on the surface of colloidal nanoparticles (NPs) have a significant impact on physiochemical properties of NPs and their interaction in biological environments. In this study, we report a one-pot aqueous synthesis of 3-mercaptopropionic acid (MPA)-functionalized CdTe/CdS/ZnS quantum dots (Qdots) in the presence of thiol-terminated methoxy polyethylene glycol (mPEG) molecules as a surface coordinating ligand. The resulting mPEG-Qdots were characterized by using ζ potential, FTIR, thermogravimetric (TG) analysis, and microscale thermophoresis (MST) studies. We investigated the effect of mPEG molecules and their grafting density on the Qdots photophysical properties, colloidal stability, protein binding affinity, and in vitro cellular toxicity. Moreover, cellular binding features of the resulting Qdots were examined by using three-dimensional (3D) tumor-like spheroids, and the results were discussed in detail. Promisingly, mPEG ligands were found to increase colloidal stability of Qdots, reduce adsorption of proteins to the Qdot surface, and mitigate Qdot-induced side effects to a great extent. Flow cytometry and confocal microscopy studies revealed that PEGylated Qdots exhibited distinctive cellular interactions with respect to their mPEG grafting density. As a result, mPEG molecules demonstrated a minimal effect on the ZnS shell deposition and the Qdot fluorescence efficiency at a low mPEG density, whereas they showed pronounced effect on Qdot colloidal stability, protein binding affinity, cytotoxicity, and nonspecific binding at a higher mPEG grafting amount.
胶体纳米颗粒（NPs）表面使用的配体对NPs的物理化学性质及其在生物环境中的相互作用有重大影响。在本研究中，我们报告了在硫醇封端的甲氧基聚乙二醇（mPEG）分子作为表面配位配体存在下，一锅水相合成3-巯基丙酸（MPA）功能化的CdTe/CdS/ZnS量子点（Qdots）。通过ζ电位、傅里叶变换红外光谱（FTIR）、热重（TG）分析和微尺度热泳（MST）研究对所得的mPEG-Qdots进行了表征。我们研究了mPEG分子及其接枝密度对Qdots光物理性质、胶体稳定性、蛋白质结合亲和力和体外细胞毒性的影响。此外，使用三维（3D）肿瘤样球体检查了所得Qdots的细胞结合特征，并对结果进行了详细讨论。有希望的是，发现mPEG配体可提高Qdots的胶体稳定性，减少蛋白质在Qdot表面的吸附，并在很大程度上减轻Qdot诱导的副作用。流式细胞术和共聚焦显微镜研究表明，聚乙二醇化的Qdots根据其mPEG接枝密度表现出独特的细胞相互作用。因此，在低mPEG密度下，mPEG分子对ZnS壳层沉积和Qdot荧光效率的影响最小，而在较高mPEG接枝量下，它们对Qdot胶体稳定性、蛋白质结合亲和力、细胞毒性和非特异性结合表现出显著影响。
