Biological Toxicity and Inflammatory Response of Semi-Single-Walled Carbon Nanotubes

The toxicological studies on carbon nanotubes (CNTs) have been urgently needed from the emerging diverse applications of CNTs. Physicochemical properties such as shape, diameter, conductance, surface charge and surface chemistry of CNTs gained during manufacturing processes play a key role in the toxicity. In this study, we separated the semi-conductive components of SWCNTs (semi-SWCNTs) and evaluated the toxicity on days 1, 7, 14 and 28 after intratracheal instillation in order to determine the role of conductance. Exposure to semi-SWCNTs significantly increased the growth of mice and significantly decreased the relative ratio of brain weight to body weight. Recruitment of monocytes into the bloodstream increased in a time-dependent manner, and significant hematological changes were observed 28 days after exposure. In the bronchoalveolar lavage (BAL) fluid, secretion of Th2-type cytokines, particularly IL-10, was more predominant than Th1-type cytokines, and expression of regulated on activation normal T cell expressed and secreted (RANTES), p53, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) increased in a time-dependent manner. Fibrotic histopathological changes peaked on day 7 and decreased 14 days after exposure. Expression of cyclooxygenase-2 (COX-2), mesothelin, and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) also peaked on day 7, while that of TGF-β peaked on days 7 and 14. Secretion of histamine in BAL fluid decreased in a time-dependent manner. Consequently, we suggest that the brain is the target organ of semi-SWCNTs brought into the lung, and conductance as well as length may be critical factors affecting the intensity and duration of the inflammatory response following SWCNT exposure.

随着碳纳米管（carbon nanotubes, CNTs）各类新兴应用的不断涌现，针对其开展毒理学研究已成为迫切需求。碳纳米管在制备过程中所形成的形貌、直径、导电性、表面电荷及表面化学性质等理化特性，对其毒性起着关键调控作用。本研究中，我们分离得到单壁碳纳米管（single-walled carbon nanotubes, SWCNTs）中的半导电组分（semi-SWCNTs），并通过气管滴注染毒后分别于第1、7、14、28天评估其毒性，以明确导电性在其中的作用。

半导电型单壁碳纳米管染毒可显著促进小鼠生长，并显著降低脑重与体重的相对比值。外周血单核细胞募集呈时间依赖性增加，且染毒后28天可观察到显著的血液学指标变化。在支气管肺泡灌洗液（bronchoalveolar lavage, BAL）中，Th2型细胞因子（尤其是白细胞介素10, IL-10）的分泌水平显著高于Th1型细胞因子；同时，活化调节正常T细胞表达和分泌因子（RANTES）、p53、转化生长因子β（TGF-β）以及诱导型一氧化氮合酶（iNOS）的表达均呈时间依赖性上调。肺纤维化样组织病理学改变于染毒后第7天达到峰值，第14天时有所缓解。环氧合酶2（COX-2）、间皮素以及磷酸化信号转导与转录激活因子3（pSTAT3）的表达同样于第7天达到峰值，而TGF-β的表达峰值则出现在第7天和第14天。支气管肺泡灌洗液中组胺的分泌呈时间依赖性下降。

综上，本研究提示吸入肺部的半导电型单壁碳纳米管可靶向作用于脑组织；且导电性与长度可能是影响单壁碳纳米管染毒后炎症反应强度与持续时间的关键因素。