Combination of small size and carboxyl functionalisation causes cytotoxicity of short carbon nanotubes

Frőhlich, Eleonore; Meindl, Claudia; Höfler, Anita; Leitinger, Gerd; Roblegg, Eva

doi:10.3109/17435390.2012.729274

Cited by 21 publications

(31 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While several studies indicated that COOH functionalization significantly decreased CNT bioactivities, e.g. fibrogenic responses and pulmonary inflammation49505152, we and some others observed an increase in cytogenic, genotoxic and fibrogenic activities by COOH functionalization5354. In the present study, f-MWCNT elicited more robust effects on CAF-like cells and CSCs as compared to MWCNT.…”

Section: Discussioncontrasting

confidence: 53%

Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity

Luanpitpong

Wang

Castranova

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Tumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells. The mechanism by which CNT-induced CAF-like cells promote tumor growth involved the acquisition of cancer stem cells (CSCs) in cancer population. Gene knockdown experiments showed that an expression of podoplanin on CAF-like cells is essential for their effects, indicating the functional role of CAF-like cells and podoplanin in CNT tumorigenic process. Our findings unveil a novel mechanism of CNT-induced carcinogenesis through the induction of CAF-like cells that support CSCs and drive tumor formation. Our results also suggest the potential utility of podoplanin as a mechanism-based biomarker for rapid screening of carcinogenicity of CNTs and related nanomaterials for their safer design.

show abstract

Section: Discussioncontrasting

confidence: 53%

Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity

Luanpitpong

Wang

Castranova

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…2012). Thinner CNTs were also found to be more cytotoxic to EAhy926, A549, HepG2, DMBM-2 V79 and TK-6 cells than thicker CNTs (Frohlich et al 2013). However, long and thick CNTs, but not short and thin MWCNTs, were shown to cause inflammation in mice (Yamashita et al 2010).…”

Section: Role Of Physico-chemical Properties Associated With Genotoximentioning

confidence: 99%

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Kuempel

Jaurand

Møller

et al. 2016

Critical Reviews in Toxicology

View full text Add to dashboard Cite

In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.

show abstract

“…CNTs, in addition to Dynamic Light Scattering, were also characterized by transmission electron microscopy and EDX analysis, as described earlier [15]. Diameters as determined by TEM were similar to what was indicated by the producer.…”

Section: Resultsmentioning

confidence: 82%

“…CNTs suspended in DMEM +10% fetal bovine serum have been characterized physicochemically by Dynamic Light Scattering and Laser Doppler Velocimetry (Nanosizer, determination of size and surface charge), transmission electron microscopy (FEI Tecnai G² 20, determination of size), and energy dispersive X-ray spectroscopy (FEI Tecnai G² 20 with Standard SUTW detector, detection of metal contamination) as described in a previous study [15]. Heavy metal contamination was shown to be below detection threshold.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Suitability of Cell-Based Label-Free Detection for Cytotoxicity Screening of Carbon Nanotubes

Meindl

Absenger

Roblegg

et al. 2013

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Cytotoxicity testing of nanoparticles (NPs) by conventional screening assays is often complicated by interference. Carbon nanotubes (CNTs) are particularly difficult to assess. To test the suitability of cell-based label-free techniques for this application, a panel of CNTs with different diameters and surface functionalizations was assessed by impedance-based technique (xCELLigence RTCA) and automated microscopy (Cell-IQ) compared to formazan bioreduction (MTS assay). For validation of the label-free systems different concentrations of ethanol and of amine (AMI) polystyrene NPs were used. CNTs were evaluated in various cell lines, but only endothelial EAhy926 cells and L929 and V79 fibroblasts could be evaluated in all systems. Polystyrene particles obtained similar results in all assays. All systems identified thin (<8 nm) CNTs as more cytotoxic than thick (>20 nm) CNTs, but detection by xCELLigence system was less sensitive to CNT-induced cytotoxicity. Despite advantages, such as continuous monitoring and more detailed analysis of cytotoxic effects, label-free techniques cannot be generally recommended for cytotoxicity screening of NPs.

show abstract

Combination of small size and carboxyl functionalisation causes cytotoxicity of short carbon nanotubes

Cited by 21 publications

References 81 publications

Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity

Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Suitability of Cell-Based Label-Free Detection for Cytotoxicity Screening of Carbon Nanotubes

Contact Info

Product

Resources

About