Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

Takanashi, Seiji; Hara, Kazuo; Aoki, Katsumi; Usui, Yuki; Shimizu, Masayuki; Haniu, Hisao; Ogihara, Nobuhide; Ishigaki, Norio; Nakamura, Kōichi; Okamoto, Masato; Kobayashi, Shinsuke; Kato, Hiroyuki; Sakai, Kenji; Nishimura, Norio; Tsutsumi, Hiromori; Machida, Kazuhiko

doi:10.1038/srep00498

Cited by 42 publications

(48 citation statements)

References 52 publications

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“…These findings implied that the toxicity of the t-ox-MWCNTs was not severe. In agreement with the relatively low toxicity of the t-ox-MWCNTs used here, a previous study reported that MWCNTs implanted into subcutaneous tissue on the backs of genetically-modified rasH2 mice were less carcinogenic than carbon black derived from tattoo ink59.…”

Section: Discussionsupporting

confidence: 90%

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

Sato

Yokoyama

Nodasaka

et al. 2013

Sci Rep

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Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials.

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Section: Discussionsupporting

confidence: 90%

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

Sato

Yokoyama

Nodasaka

et al. 2013

Sci Rep

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“…The other dispersant, PS, was selected because it is typically used as the dispersant for CNTs [28,29]. Our lab has also used PS for in vivo experiments, mainly to avoid provoking an immunoresponse [30,31,32]. Our results showed that PS showed better dispersibility than FBS, using the PR-1.…”

Section: Discussionmentioning

confidence: 88%

The Dispersion State of Tangled Multi-Walled Carbon Nanotubes Affects Their Cytotoxicity

et al. 2016

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The medical applications of carbon nanotubes (CNTs) have garnered much attention. However, evaluating the safety of CNTs remains difficult, and no consensus has been reached. Moreover, assessing the biosafety of multi-walled CNTs (MWCNTs), which can become tangled during manufacturing, is challenging because they do not readily disperse. We studied how the dispersion state of tangled MWCNTs affects their cytotoxicity, using three sonicators. Flotube 9110 (FT9110), tangled MWCNTs, were dispersed in two dispersants (fetal bovine serum and polysorbate 80) using a new type of sonicator (PR-1) and two conventional sonicators. The size and cytotoxicity of the dispersed FT9110 were measured using the BEAS-2B human bronchial epithelial cell line. The PR-1 dispersed the FT9110 to agglomerates <200 nm in diameter; FT9110 dispersed with the PR-1 did not show cytotoxicity regardless of dispersant. The other sonicators dispersed the FT9110 to particles >1000 nm in diameter, and cytotoxicity depended on the dispersant. We found that excluding cells adhered to agglomerated FT9110 before evaluating cytotoxicity can lead to false-positive results. The PR-1 sonicator dispersed tangled FT9110 to many single fibers, which showed lower cytotoxicity than conventionally-sonicated MWCNTs. We suggest that dispersion state should be accounted for when evaluating the cytotoxicity of MWCNTs.

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“…It is also important to differentiate between the confounding results of toxicity tests designed to determine the effect of accidental exposure to CNTs from tests involving intentional exposure to CNTs which have been modified for biomedical applications [61]. For example, toxicity tests involving very long, pristine CNTs similar to raw material used for industrial purposes demonstrate the potential carcinogenicity of CNTs [62], while CNTs functionalized for biomedical applications, such as those used in our study, are not carcinogenic [63]. …”

Section: Discussionmentioning

confidence: 99%

Targeting Breast Cancer with Sugar-Coated Carbon Nanotubes

Fahrenholtz

Hadimani

King

et al. 2015

Nanomedicine (Lond.)

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Aims To evaluate the use of glucosamine functionalized multiwalled carbon nanotubes (glyco-MWCNTs) for breast cancer targeting. Materials & methods Two types of glucosamine functionalized MWCNTs were developed (covalently linked glucosamine and non-covalently phospholipid-glucosamine coated) and evaluated for their potential to bind and target breast cancer cells in vitro and in vivo. Results & conclusion Binding of glyco-MWCNTs in breast cancer cells is mediated by specific interaction with glucose transporters. Glyco-MWCNTs prepared by non-covalent coating with phospholipid-glucosamine displayed an extended blood circulation time, delayed urinary clearance, low tissue retention and increased breast cancer tumor accumulation in vivo. These studies lay the foundation for development of a cancer diagnostic agent based upon glyco-MWCNTs with the potential for superior accuracy over current radiopharmaceuticals.

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Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

Cited by 42 publications

References 52 publications

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

The Dispersion State of Tangled Multi-Walled Carbon Nanotubes Affects Their Cytotoxicity

Targeting Breast Cancer with Sugar-Coated Carbon Nanotubes

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