Lee Soyoung, Khang Dongwoo, Kim Sang-Hyun
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Department of Molecular Medicine, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
Int J Nanomedicine. 2015 Apr 1;10:2697-710. doi: 10.2147/IJN.S80836. eCollection 2015.
From the various physiochemical material properties, the chemical functionalization order of single-walled carbon nanotubes (swCNTs) has not been considered as a critical factor for modulating immunological responses and toxicological aspects in drug delivery applications. Although most nanomaterials, including carbon nanotubes, are specifically accumulated in spleen, few studies have focused on spleen immunotoxicity. For this reason, this study demonstrated that the dispersity of swCNTs significantly influenced immunotoxicity in vitro and in vivo.
For cytotoxicity of swCNTs, MTT assay, reactive oxygen species production, superoxide dismutase activity, cellular uptake, and confocal microscopy were used in macrophages. In the in vivo study, female BALB/c mice were intravenously administered with 1 mg/kg/day of swCNTs for 2 weeks. The body weight, organ weight, hematological change, reverse-transcription polymerase chain reaction, and lymphocyte population were evaluated.
Different orders of chemical functionalization of swCNTs controlled immunotoxicity. In short, less-dispersed swCNTs caused cytotoxicity in macrophages and abnormalities in immune organs such as spleen, whereas highly dispersed swCNTs did not result in immunotoxicity.
This study clarified that increasing carboxyl groups on swCNTs significantly mitigated immunotoxicity in vitro and in vivo. Our findings clarified the effective immunotoxicological factors of swCNTs by increasing dispersity of swCNTs and provided useful guidelines for the effective use of nanomaterials.
从各种物理化学材料特性来看,单壁碳纳米管(swCNTs)的化学功能化顺序在药物递送应用中尚未被视为调节免疫反应和毒理学方面的关键因素。尽管包括碳纳米管在内的大多数纳米材料会在脾脏中特异性蓄积,但很少有研究关注脾脏免疫毒性。因此,本研究表明swCNTs的分散性在体外和体内均显著影响免疫毒性。
对于swCNTs的细胞毒性,在巨噬细胞中采用MTT法、活性氧生成、超氧化物歧化酶活性、细胞摄取和共聚焦显微镜观察。在体内研究中,雌性BALB/c小鼠静脉注射1mg/kg/天的swCNTs,持续2周。评估体重、器官重量、血液学变化、逆转录聚合酶链反应和淋巴细胞群体。
swCNTs不同的化学功能化顺序控制着免疫毒性。简而言之,分散性较差的swCNTs会导致巨噬细胞毒性以及脾脏等免疫器官的异常,而高度分散的swCNTs不会导致免疫毒性。
本研究阐明,增加swCNTs上的羧基可显著减轻体外和体内的免疫毒性。我们的研究结果通过提高swCNTs的分散性阐明了其有效的免疫毒理学因素,并为纳米材料的有效利用提供了有用的指导方针。