CBET Research Group, Dept. Zoology and Animal Cell Biology; Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country, Spain.
EU Commission-Joint Research Centre, Institute of Health and Consumer Protection, NSB Unit, Ispra (VA), Italy.
Aquat Toxicol. 2014 Aug;153:39-52. doi: 10.1016/j.aquatox.2014.02.003. Epub 2014 Feb 14.
CdS quantum dots (QDs) show a great promise for treatment and diagnosis of cancer and for targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. In spite of their advantages it is important to determine if CdS QDs can exert toxicity on biological systems. In the present work, cytotoxicity of CdS QDs (5 nm) at a wide range of concentrations (0.001-100 mg Cd/L) was screened using neutral red (NR) and thiazolyl blue tetrazolium bromide (MTT) assays in isolated hemocytes and gill cells of mussels (Mytilus galloprovincialis). The mechanisms of action of CdS QDs were assessed at sublethal concentrations (0.31-5 mg Cd/L) in the same cell types through a series of functional in vitro assays: production of reactive oxygen species (ROS), catalase (CAT) activity, DNA damage, lysosomal acid phosphatase (AcP) activity, multixenobiotic resistance (MXR) transport activity, Na-K-ATPase activity (only in gill cells) and phagocytic activity and damage to actin cytoskeleton (only in hemocytes). Exposures to CdS QDs lasted for 24h and were performed in parallel with exposures to bulk CdS and ionic Cd. Ionic Cd was the most toxic form to both cell types, followed by CdS QDs and bulk CdS. ROS production, DNA damage, AcP activity and MXR transport were significantly increased in both cell types exposed to the 3 forms of Cd. CAT activity increased in hemocytes exposed to the three forms of Cd while in gill cells only in those exposed to ionic Cd. No effects were found on hemocytes cytoskeleton integrity. Effects on phagocytosis were found in hemocytes exposed to bulk CdS and to CdS QDs at concentrations equal or higher than 1.25 mg Cd/L but not in those exposed to ionic Cd, indicating a particle-specific effect on phagocytosis. In conclusion, cell-mediated immunity and gill cell function represent significant targets for CdS QDs toxicity.
CdS 量子点（QDs）由于其可调荧光和易于进行组织靶向功能化，在癌症的治疗和诊断以及靶向药物输送方面具有广阔的应用前景。尽管它们具有优势，但重要的是要确定 CdS QDs 是否会对生物系统产生毒性。在本工作中，使用中性红（NR）和噻唑蓝（MTT）测定法，在贻贝（Mytilus galloprovincialis）的分离血细胞和鳃细胞中筛选了宽浓度范围（0.001-100 mg Cd/L）的 CdS QDs（5nm）的细胞毒性。在相同的细胞类型中，在亚致死浓度（0.31-5mg Cd/L）下，通过一系列功能体外测定法评估了 CdS QDs 的作用机制：活性氧（ROS）的产生、过氧化氢酶（CAT）活性、DNA 损伤、溶酶体酸性磷酸酶（AcP）活性、多药耐药（MXR）转运活性、Na-K-ATPase 活性（仅在鳃细胞中）和吞噬活性以及肌动蛋白细胞骨架损伤（仅在血细胞中）。CdS QDs 的暴露时间为 24h，并与对大块 CdS 和离子 Cd 的暴露同时进行。离子 Cd 对两种细胞类型均具有毒性，其次是 CdS QDs 和大块 CdS。暴露于 3 种 Cd 形式的两种细胞类型的 ROS 产生、DNA 损伤、AcP 活性和 MXR 转运均显著增加。暴露于 3 种 Cd 形式的血细胞中的 CAT 活性增加，而仅在暴露于离子 Cd 的鳃细胞中增加。未发现血细胞细胞骨架完整性受到影响。在暴露于大块 CdS 和 CdS QDs（浓度等于或高于 1.25mg Cd/L）的血细胞中发现了吞噬作用的变化，但在暴露于离子 Cd 的血细胞中未发现这种变化，表明吞噬作用具有颗粒特异性。总之，细胞介导的免疫和鳃细胞功能是 CdS QDs 毒性的重要靶标。
