Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300, USA.
J Toxicol Environ Health A. 2012;75(2):112-28. doi: 10.1080/15287394.2011.615110.
Multiwalled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level.
多壁碳纳米管(MWCNT)由于其非凡的物理、化学和光学特性,在生物医学应用中引起了极大的兴趣。已经在动物模型中使用了基于 MWCNT 的医学成像剂和药物的静脉内给药。然而,MWCNT 给药对人类潜在的有害健康影响尚未阐明。此外,迄今为止,关于 MWCNT 从血液循环转移到靶组织和器官的确切机制,尚无明显报道。本研究表明,暴露于 MWCNT 会导致人微血管内皮细胞(HMVEC)的细胞通透性增加。本研究的结果还表明,MWCNT 诱导的内皮通透性增加是由活性氧(ROS)产生和肌动蛋白丝重塑介导的。此外,发现 MWCNT 促进了 HMVEC 中的细胞迁移。在机制上,MWCNT 暴露会增加 HMVEC 中单核细胞趋化蛋白 1(MCP-1)和细胞间黏附分子 1(ICAM-1)的水平。总之,这些结果为 MWCNT 的生物反应性提供了新的见解,这可能对 MWCNT 在血管靶向、成像和药物输送中的生物医学应用具有重要意义。本研究的结果还阐明了 MWCNT 暴露在细胞水平上对人类的潜在不利影响。