Soenen Stefaan J, Manshian Bella B, Aubert Tangi, Himmelreich Uwe, Demeester Jo, De Smedt Stefaan C, Hens Zeger, Braeckmans Kevin
MoSAIC/Biomedical NMR Unit, Department of Medicine, Catholic University of Leuven , Herestraat 49, B3000 Leuven, Belgium.
Chem Res Toxicol. 2014 Jun 16;27(6):1050-9. doi: 10.1021/tx5000975. Epub 2014 Jun 4.
The use of quantum dots (QDots) as bright and photostable probes for long-term fluorescence imaging is gaining more interest. Thus far, (pre)clinical use of QDots remains limited, which is primarily caused by the potential toxicity of QDots. Most QDots consist of Cd2+ ions, which are known to cause high levels of toxicity. In order to overcome this problem, several strategies have been tested, such as the generation of cadmium-free QDots. In the present study, two types of cadmium-free QDots, composed of ZnSe/ZnS (QDotZnSe) and InP/ZnS (QDotInP), were studied with respect to their cytotoxicity and cellular uptake in a variety of cell types. A multiparametric cytotoxicity approach is used, where the QDots are studied with respect to cell viability, oxidative stress, cell morphology, stem cell differentiation, and neurite outgrowth. The data reveal slight differences in uptake levels for both types of QDots (maximal for QDotZnSe), but clear differences in cytotoxicity and cell functionality effects exist, with highest toxicity for QDotZnSe. Differences between cell types and between both types of QDots can be explained by the intrinsic sensitivity of certain cell types and chemical composition of the QDots. At concentrations at which no toxic effects can be observed, the functionality of the QDots for fluorescence cell visualization is evaluated, revealing that the higher brightness of QDotZnSe overcomes most of the toxicity issues compared to that of QDotInP. Comparing the results obtained with common Cd2+-containing QDots tested under identical conditions, the importance of particle functionality is demonstrated, revealing that cadmium-free QDots tested in this study are not significantly better than Cd2+-containing QDots for long-term cell imaging and that more work needs to be performed in optimizing the brightness and surface chemistry of cadmium-free QDots for them to replace currently used Cd2+-containing QDots.
量子点（QDots）作为用于长期荧光成像的明亮且光稳定的探针，正受到越来越多的关注。到目前为止，量子点在（临床前）临床中的应用仍然有限，这主要是由量子点的潜在毒性所致。大多数量子点由镉离子（Cd2+）组成，已知这些离子会导致高毒性。为了克服这个问题，已经测试了几种策略，例如生成无镉量子点。在本研究中，对两种类型的无镉量子点，即由ZnSe/ZnS组成的量子点（QDotZnSe）和由InP/ZnS组成的量子点（QDotInP），在多种细胞类型中的细胞毒性和细胞摄取情况进行了研究。采用了多参数细胞毒性方法，研究量子点在细胞活力、氧化应激、细胞形态、干细胞分化和神经突生长方面的情况。数据显示，两种类型的量子点在摄取水平上存在细微差异（QDotZnSe的摄取量最大），但在细胞毒性和细胞功能效应方面存在明显差异，其中QDotZnSe的毒性最高。细胞类型之间以及两种类型的量子点之间的差异可以通过某些细胞类型的内在敏感性和量子点的化学成分来解释。在未观察到毒性作用的浓度下，评估了量子点用于荧光细胞可视化的功能，结果表明，与QDotInP相比，QDotZnSe的较高亮度克服了大部分毒性问题。将在相同条件下测试的普通含镉量子点所获得的结果进行比较，证明了颗粒功能的重要性，结果表明，本研究中测试的无镉量子点在长期细胞成像方面并不比含镉量子点显著更好，并且需要开展更多工作来优化无镉量子点的亮度和表面化学性质，以便它们能够取代目前使用的含镉量子点。
