title: Functionalized single-walled carbon nanotubes cause reversible acute lung injury and induce fibrosis in mice.
abstract: Nanotechnology is one of today's most promising technological developments, but safety concerns raise questions about its development. Risk assessments of nanomaterials during occupational exposure are crucial for their development. Here, we assessed the lung toxicity of functionalized single-walled carbon nanotube (f-SWCNT) exposure in C57BL/6 mice, elucidated the underlying molecular mechanism, and evaluated the self-repair ability and lung fibrosis of the mice. Soluble f-SWCNTs were administered to mice. After 18 h or 14 days, the lung histopathology, bronchoalveolar lavage fluid, lung edema, vascular permeability, and PaO(2) levels were evaluated, and biochemical and immunostaining tests were also performed. We found that some f-SWCNTs could induce acute lung injury (ALI) in mice via proinflammatory cytokine storm signaling through the NF-κB pathway in vivo. We illustrated that corticosteroid treatments could ameliorate the ALI induced by the f-SWCNTs in mice. Surprisingly, the ALI was almost completely reversed within 14 days, while mild to moderate fibrosis, granuloma, and DNA damage remained in the mice at day 14. Our studies indicate potential remedies to address the growing concerns about the safety of nanomaterials. In addition, we notify that the type of functional groups should be considered in nanomedicine application as differently functionalized SWCNTs generated different effects on the lung toxicity.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Chengyu Jiang, Room 460, No. 5 Dongdansantiao, Beijing 100005, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiejie
authors.initials: J
authors.lastname: Deng
authors.forename: Yanxu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Chenggang
authors.initials: C
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zou
authors.forename: Wen
authors.initials: W
authors.lastname: Xi
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Han
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008156:Luciferases; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000009:adverse effects*; D010316:Particle Size; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D016328:NF-kappa B; D037742:Nanotubes, Carbon; D003907:Dexamethasone; D008156:Luciferases