Ding Yun, Tian Rong, Yang Zhen, Chen Jianfa, Lu Naihao
Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
Department of Physics, University of Houston, Houston, TX, USA.
Biophys Chem. 2017 Mar;222:1-6. doi: 10.1016/j.bpc.2016.12.002. Epub 2016 Dec 23.
Neutrophil myeloperoxidase (MPO) and peroxynitrite (ONOO) can oxidatively biodegrade carboxylated single-walled carbon nanotubes (SWCNTs). The protein-SWCNTs interactions will play an important role in the degradation and cytotoxicity of nanotubes. Here, we investigated the binding of bovine serum albumin (BSA, a common and well-characterized model blood serum protein) to SWCNTs, and found that the hydrophobic and electrostatic interactions might be crucial factors in stabilizing the binding of SWCNTs with BSA. The binding of BSA could impair SWCNTs biodegradation in vitro through the competitive adsorption to nanotube. Both SWCNTs and BSA-SWCNTs were significantly degraded in zymosan-stimulated macrophages, and the degradation degree was more for BSA-SWCNTs. The mechanism for SWCNTs degradation in activated macrophages was further investigated to demonstrate the dominant participation of MPO and ONOO-driven pathways. Moreover, binding of BSA to SWCNTs reduced cytotoxicity and degraded nanotubes induced less cytotoxicity than non-degraded nanotubes. The binding of BSA may be an important determinant for the biodegradation and cytotoxicity of SWCNTs in inflammatory cells, and therefore, provide a new route to mitigate the potential toxicity of nanotubes in future biomedical applications.
中性粒细胞髓过氧化物酶（MPO）和过氧亚硝酸盐（ONOO）可氧化生物降解羧基化单壁碳纳米管（SWCNT）。蛋白质与SWCNT的相互作用将在纳米管的降解和细胞毒性中发挥重要作用。在此，我们研究了牛血清白蛋白（BSA，一种常见且特性明确的模型血清蛋白）与SWCNT的结合，发现疏水和静电相互作用可能是稳定SWCNT与BSA结合的关键因素。BSA的结合可通过对纳米管的竞争性吸附损害体外SWCNT的生物降解。在酵母聚糖刺激的巨噬细胞中，SWCNT和BSA-SWCNT均显著降解，且BSA-SWCNT的降解程度更高。进一步研究了活化巨噬细胞中SWCNT降解的机制，以证明MPO和ONOO驱动途径的主要参与。此外，BSA与SWCNT的结合降低了细胞毒性，且降解的纳米管比未降解的纳米管诱导的细胞毒性更小。BSA的结合可能是炎症细胞中SWCNT生物降解和细胞毒性的重要决定因素，因此，为减轻纳米管在未来生物医学应用中的潜在毒性提供了一条新途径。
