Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium; Ghent Research Group on Nanomedicines, Ghent University, Ottergemsesteenweg 460, B9000 Ghent, Belgium.
Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, Catholic University of Leuven, Faculty of Medicine, UZ Herestraat 49 Box 7003, B3000 Leuven, Belgium.
Acta Biomater. 2017 Jan 15;48:195-205. doi: 10.1016/j.actbio.2016.10.022. Epub 2016 Oct 17.
In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' Quantum Dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties. We carefully examined the toxicity of two identical gradient alloyed QDs, differing only in their surface coatings, namely 3-mercaptopropionic (MPA) acid and polyethylene glycol (PEG). Next to more conventional toxicological endpoints like cytotoxicity and oxidative stress, we examined the influence of these QDs on the autophagy pathway. Our study shows that the cellular effects induced by QDs on HeLa cells were strongly dictated by the surface coat of the otherwise identical particles. MPA-coated QDs proved to be highly biocompatible as a result of lysosomal activation and ROS reduction, two cellular responses that help the cell to cope with nanomaterial-induced stress. In contrast, PEGylated QDs were significantly more toxic due to increased ROS production and lysosomal impairment. This impairment next results in autophagy dysfunction which likely adds to their toxic effects. Taken together, our study shows that coating QDs with MPA is a better strategy than PEGylation for long term cell tracking with minimal cytotoxicity.
Gradient alloyed Quantum Dots (GA-QDs) are highly promising nanomaterials for biomedical imaging seeing they exhibit supremely fluorescent properties over conventional QDs. The translation of these novel QDs to the clinic requires a detailed toxicological examination, though the data on this is very limited. We therefore applied a systematic approach to examine the toxicity of GA-QDs coated with two commonly applied surface ligands, this while focusing on the autophagy pathway. The impact of QDs on this pathway is of importance since it has been connected with various diseases, including cancer. Our data accentuates that the coating defines the impact on autophagy and therefore the toxicity induced by QDs on cells: while MPA coated QDs were highly biocompatible, PEGylated QDs were toxic.
在过去的十年中，人们对自噬的兴趣大幅增加，这一现象迅速成为一个广泛的研究领域。有趣的是，人们提出这种细胞质清除系统的功能障碍是包括癌症在内的多种疾病的根源。因此，我们认为从毒理学的角度来看，研究开发用于生物医学应用的纳米材料是否会干扰这一细胞过程至关重要。在这里，我们研究了极有前途的“梯度合金量子点”（QD），它们与传统的量子点不同，其核心组成呈梯度分布，从而具有更好的荧光特性。我们仔细研究了两种相同的梯度合金量子点的毒性，这两种量子点仅在其表面涂层上有所不同，即 3-巯基丙酸（MPA）和聚乙二醇（PEG）。除了细胞毒性和氧化应激等更传统的毒理学终点外，我们还研究了这些 QD 对自噬途径的影响。我们的研究表明，QD 对 HeLa 细胞的细胞效应强烈取决于表面涂层，而颗粒的其他方面则相同。MPA 涂层的 QD 由于溶酶体的激活和 ROS 的减少而表现出高度的生物相容性，这两种细胞反应有助于细胞应对纳米材料诱导的应激。相比之下，由于 ROS 生成和溶酶体损伤增加，PEG 化的 QD 毒性更大。这种损伤接下来导致自噬功能障碍，这可能会增加其毒性作用。总的来说，我们的研究表明，用 MPA 对 QD 进行涂层处理是一种比 PEG 化更好的策略，可用于长期细胞追踪，且细胞毒性最小。
