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羧酸官能化可防止预测的环境相关浓度下的多壁碳纳米管向线虫秀丽隐杆线虫的靶器官转移。

Carboxylic acid functionalization prevents the translocation of multi-walled carbon nanotubes at predicted environmentally relevant concentrations into targeted organs of nematode Caenorhabditis elegans.

机构信息

Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing 210009, China.

出版信息

Nanoscale. 2013 Jul 7;5(13):6088-96. doi: 10.1039/c3nr00847a. Epub 2013 May 30.

Abstract

Carboxyl (-COOH) surface modified multi-walled carbon nanotubes (MWCNTs-COOH) can be used for targeted delivery of drugs and imaging. However, whether MWCNTs-COOH at environmentally relevant concentrations exert certain toxic effects on multicellular organisms and the underlying mechanisms are still largely unclear. In the present study, we applied the nematode Caenorhabditis elegans to evaluate the properties of MWCNTs-COOH at environmentally relevant concentrations by comparing the effects of MWCNTs and MWCNTs-COOH exposure on C. elegans from L1-larvae to adult at concentrations of 0.001-1000 μg L(-1). Exposure to MWCNTs could potentially damage the intestine (primary targeted organ) at concentrations greater than 0.1 μg L(-1) and functions of neurons and reproductive organ (secondary targeted organs) at concentrations greater than 0.001 μg L(-1). Carboxyl modification prevented the toxicity of MWCNTs on the primary and the secondary targeted organs at concentrations less than 100 μg L(-1), suggesting that carboxyl modification can effectively prevent the adverse effects of MWCNTs at environmentally relevant concentrations. After exposure, MWCNTs-COOH (1 mg L(-1)) were translocated into the spermatheca and embryos in the body through the primary targeted organs. However, MWCNTs-COOH (10 μg L(-1)) were not observed in spermatheca and embryos in the body of nematodes. Moreover, relatively high concentrations of MWCNTs-COOH exposed nematodes might have a hyper-permeable intestinal barrier, whereas MWCNTs-COOH at environmentally relevant concentrations effectively sustained the normally permeable state for the intestinal barrier. Therefore, we elucidated the cellular basis of carboxyl modification to prevent toxicity of MWCNTs at environmentally relevant concentrations. Our data highlights the key role of biological barriers in the primary targeted organs to block toxicity formation from MWCNTs, which will be useful for the design of effective prevention strategies against MWCNTs toxicity.

摘要

羧基(-COOH)表面修饰的多壁碳纳米管(MWCNTs-COOH)可用于药物的靶向递送和成像。然而,在环境相关浓度下,MWCNTs-COOH 是否对多细胞生物产生某些毒性作用,以及其潜在的作用机制尚不清楚。在本研究中,我们应用秀丽隐杆线虫来评估 MWCNTs-COOH 在环境相关浓度下的性质,比较了 MWCNTs 和 MWCNTs-COOH 暴露对 L1 幼虫至成虫的秀丽隐杆线虫的影响,浓度范围为 0.001-1000μg/L。暴露于 MWCNTs 可能会在浓度大于 0.1μg/L 时对肠道(主要靶向器官)造成潜在损伤,在浓度大于 0.001μg/L 时对神经元和生殖器官(次要靶向器官)造成功能损伤。羧基修饰在浓度低于 100μg/L 时可以防止 MWCNTs 对主要和次要靶向器官的毒性,表明羧基修饰可以有效防止 MWCNTs 在环境相关浓度下的不良影响。暴露后,MWCNTs-COOH(1mg/L)通过主要靶向器官转运到生殖腺和体内的胚胎中。然而,在体内的生殖腺和胚胎中没有观察到 10μg/L 的 MWCNTs-COOH。此外,暴露于相对较高浓度的 MWCNTs-COOH 的线虫可能具有渗透性过高的肠屏障,而环境相关浓度的 MWCNTs-COOH 则有效地维持了肠屏障的正常渗透性状态。因此,我们阐明了羧基修饰防止 MWCNTs 在环境相关浓度下毒性的细胞基础。我们的数据强调了生物屏障在主要靶向器官中的关键作用,以阻止 MWCNTs 毒性的形成,这对于设计有效的 MWCNTs 毒性预防策略将是有用的。

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