多壁碳纳米管致癌性的研究进展

doi:10.3969/j.issn.1004-616x.2014.03.019

摘要/Abstract

摘要：

多壁碳纳米管(MWCNT)是目前最常用的纳米材料之一。MWCNT具有大比表面积、高纵横比和管状结构的特点，与生物体内许多重要的大分子如DNA、蛋白质等具有高度亲和力，可以在体内多个器官间游走且不易降解排出。目前MWCNT在医学人工材料、疾病诊断甚至肿瘤治疗等方面得到广泛使用，但是其长期大规模使用是否会对机体造成毒性损伤甚至导致癌症发生尚无定论。本文就MWCNT的致癌性研究进展作一综述，为进一步阐明MWCNT的毒性损伤及其机制提供线索。

关键词: 多壁碳纳米管, 致癌性, 细胞毒性, 体内毒性

鞠莉，朱丽瑾，杨军. 多壁碳纳米管致癌性的研究进展[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2014.03.019.

参考文献

[1] Ali-Boucetta H，Al-Jamal KT，McCarthy D，et al. Multi-walled carbon nanotube-doxorubicin supramolecular complexes for cancer therapeutics[J]. Chem Commun：Camb， 2008， (4)：459-461.

[2] Wu W，Li R，Bian X，et al. Covalently combining carbon nanotubes with anticancer agent：preparation and antitumor activity[J]. ACS Nano，2009，3(9)：2740-2750.

[3] Kam NW，O'Connell M，Wisdom JA，et al. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction[J]. Proc Natl Acad Sci USA，2005，102(33)：11600-11605.

[4] Ding L，Stilwell J，Zhang T，et al. Molecular characterization of the cytotoxic mechanism of multiwall carbon nanotubes and nano-onions on human skin fibroblast[J]. Nano Lett，2005， 5(12)：2448-2464.

[5] Walker VG，Li Z，Hulderman T，et al. Potential in vitro effects of carbon nanotubes on human aortic endothelial cells[J]. Toxicol Appl Pharmacol，2009，236(3)：319-328.

[6] Pacurari M，Qian Y，Fu W，et al. Cell permeability， migration，and reactive oxygen species induced by multiwalled carbon nanotubes in human microvascular endothelial cells[J]. J Toxicol Environ Health A，2012，75(2)：112-128.

[7] Muller J，Decordier I，Hoet PH，et al. Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells[J]. Carcinogenesis，2008，29(2)：427-433.

[8] Kermanizadeh A，Vranic S，Boland S，et al. An in vitro assessment of panel of engineered nanomaterials using a human renal cell line：cytotoxicity，pro-inflammatory response， oxidative stress and genotoxicity[J]. BMC Nephrol，2013，14： 96.

[9] Lindberg HK，Falck GC，Singh R，et al. Genotoxicity of short single-wall and multi-wall carbon nanotubes in human bronchial epithelial and mesothelial cells in vitro[J]. Toxicology，2013，313(1)：24-37.

[10] Wirnitzer U，Herbold B，Voetz M，et al. Studies on the in vitro genotoxicity of baytubes，agglomerates of engineered multi-walled carbon-nanotubes (MWCNT)[J]. Toxicol Lett， 2009，186(3)：160-165.

[11] Szendi K，Varga C. Lack of genotoxicity of carbon nanotubes in a pilot study[J]. Anticancer Res，2008，28(1A)：349-352.

[12] Muller J，Huaux F，Moreau N，et al. Respiratory toxicity of multi-wall carbon nanotubes[J]. Toxicol Appl Pharmacol， 2005，207(3)：221-231.

[13] Ryman-Rasmussen JP，Cesta MF，Brody AR，et al. Inhaled carbon nanotubes reach the subpleural tissue in mice[J]. Nat Nanotechnol，2009，4(11)：747-751.

[14] Kato T，Totsuka Y，Ishino K，et al. Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems[J]. Nanotoxicology，2013，7(4)：452-461.

[15] Patlolla AK，Hussain SM，Schlager JJ，et al. Comparative study of the clastogenicity of functionalized and nonfunctionalized multiwalled carbon nanotubes in bone marrow cells of Swiss-Webster mice[J]. Environ Toxicol，2010， 25(6)：608-621.

[16] Mercer RR，Hubbs AF，Scabilloni JF，et al. Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes[J]. Part Fibre Toxicol，2010，7(1)：28.

[17] Takagi A，Hirose A，Nishimura T，et al. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube[J]. J Toxicol Sci，2008，33(1)： 105-116.

[18] Takagi A，Hirose A，Futakuchi M，et al. Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice[J]. Cancer Sci，2012，103(8)：1440-1444.

[19] Yamashita K，Yoshioka Y，Higashisaka K，et al. Carbon nanotubes elicit DNA damage and inflammatory response relative to their size and shape[J]. Inflammation，2010， 33(4)：276-280.

[20] Nagai H，Okazaki Y，Chew SH，et al. Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis[J]. Proc Natl Acad Sci U S A，2011， 108(49)：1330-1338.

[21] Sakamoto Y，Nakae D，Fukumori N，et al. Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats[J]. J Toxicol Sci，2009，34(1)：65-76.

[22] Porter DW，Hubbs AF，Mercer RR，et al. Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes[J]. Toxicology，2010，269(2/3)： 136-147.

[23] Yamaguchi A，Fujitani T，Ohyama K，et al. Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice[J]. J Toxicol Sci，2012，37(1)：177-189.

[24] Yu YY，Pinsky PF，Caporaso NE，et al. Lung cancer risk following detection of pulmonary scarring by chest radiography in the prostate，lung，colorectal，and ovarian cancer screening trial[J]. Arch Intern Med，2008，168(21)：2326-2332.

[25] Auerbach O，Garfinkel L，Parks VR. Scar cancer of the lung：increase over a 21 year period[J]. Cancer，1979， 43(2)：636-642.

[26] Sakai S，Ono M，Nishio T，et al. Lung cancer associated with diffuse pulmonary fibrosis：CT-pathologic correlation[J]. J Thorac Imaging，2003，18(2)：67-71.

[27] Muller J，Delos M，Panin N，et al. Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat[J]. Toxicol Sci，2009，110(2)： 442-448.

[28] Takanashi S，Hara K，Aoki K，et al. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice[J]. Sci Rep，2012，2：498.

[29] He X，Young SH，Schwegler-Berry D，et al. Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production，activating NF-kappaB signaling，and promoting fibroblast-to-myofibroblast transformation [J]. Chem Res Toxicol，2011，24(12)：2237-2248.

[30] Hazani M，Naaman R，Hennrich F，et al. Confocal fluorescence imaging of DNA-functionalized carbon nanotubes [J]. Nano Letters，2003，3(2)：153-155.

[31] Singh R，Pantarotto D，McCarthy D，et al. Binding and condensation of plasmid DNA onto functionalized carbon nanotubes：toward the construction of nanotube-based gene delivery vectors[J]. J Am Chem Soc，2005，127(12)：4388-4396.