Jeong Jiyoung, Kim Sung-Hyun, Lee Seonghan, Lee Dong-Keon, Han Youngju, Jeon Soyeon, Cho Wan-Seob
Laboratory of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, South Korea.
Front Pharmacol. 2018 Jan 22;9:15. doi: 10.3389/fphar.2018.00015. eCollection 2018.
The main mechanism of toxicity for fast-dissolving nanoparticles (NPs) is relatively simple as it originates from the intrinsic toxicity of their constituent elements rather than complicated surface reactivity. However, there is little information about the compared toxicity of fast-dissolving NP and its constituent ion, which is essential for understanding the mechanism of NP toxicity and the development of a structure-toxicity relationship (STR) model. Herein, we selected three types of fast-dissolving metal-oxide NPs (CoO, CuO, and ZnO) and constituent metal chlorides (CoCl, CuCl, and ZnCl) to compare dose-response curves between NP and its constituent metal. These materials were treated relevant cell lines for inhalation setting (i.e., differentiated THP-1 cells for macrophages and A549 cells for alveolar epithelial cells) and cytotoxicity as an endpoint was evaluated at 24 h post-incubation. The results showed that CoO and CuO NPs in both cell types showed similar patterns of dose-response curves and cytotoxic potential compared to that of their respective metal chloride. On the other hand, ZnO NPs in both cell types showed a completely different dose-response curve compared to that of ZnCl: ZnO NPs showed modest slope and much less potential for cytotoxicity compared to that of ZnCl. These results imply that fast-dissolving metal-oxide NPs are not always have similar dose-response curves and toxic potentials compared to their constituent metal chlorides and this may be due to the differential mechanism of intracellular uptake of these substances and their interaction with intracellular detoxification molecules. Further investigations are needed for the use of toxic potential of metal ions as a predicting factors of fast-dissolving NPs toxicity. In addition, chelating agent specific for dissolved metal ions can be applied for the treatment of these fast-dissolving NPs.
快速溶解纳米颗粒（NPs）的主要毒性机制相对简单，因为它源于其组成元素的内在毒性，而非复杂的表面反应性。然而，关于快速溶解纳米颗粒与其组成离子的相对毒性的信息很少，而这对于理解纳米颗粒毒性机制和建立结构-毒性关系（STR）模型至关重要。在此，我们选择了三种类型的快速溶解金属氧化物纳米颗粒（CoO、CuO和ZnO）及其组成金属氯化物（CoCl、CuCl和ZnCl），以比较纳米颗粒与其组成金属之间的剂量-反应曲线。将这些材料用于吸入环境下的相关细胞系（即用于巨噬细胞的分化THP-1细胞和用于肺泡上皮细胞的A549细胞），并在孵育24小时后评估以细胞毒性作为终点。结果表明，与各自的金属氯化物相比，两种细胞类型中的CoO和CuO纳米颗粒均显示出相似的剂量-反应曲线模式和细胞毒性潜力。另一方面，两种细胞类型中的ZnO纳米颗粒与ZnCl相比显示出完全不同的剂量-反应曲线：与ZnCl相比，ZnO纳米颗粒的斜率适中且细胞毒性潜力小得多。这些结果表明，快速溶解的金属氧化物纳米颗粒与其组成金属氯化物相比，并不总是具有相似的剂量-反应曲线和毒性潜力，这可能是由于这些物质细胞内摄取的差异机制及其与细胞内解毒分子的相互作用所致。需要进一步研究将金属离子的毒性潜力用作快速溶解纳米颗粒毒性的预测因素。此外，针对溶解金属离子的螯合剂可用于治疗这些快速溶解的纳米颗粒。
