Toxicity determinants of multi-walled carbon nanotubes: The relationship between functionalization and agglomeration

Allegri, Manfredi; Perivoliotis, Dimitrios K.; Bianchi, Massimiliano G.; Chiu, Martina; Pagliaro, Alessandra; Koklioti, Malamatenia A.; Trompeta, Aikaterini-Flora; Bergamaschi, Enrico; Bussolati, Ovidio; Charitidis, Costas A.

doi:10.1016/j.toxrep.2016.01.011

Cited by 154 publications

(110 citation statements)

References 69 publications

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“…A possible explanation is that increasing the diameter increases the bioactivity and induces significant immune response, which is consistent with previous studies showing that longer MWCNT are more bioactive. 43 Studies have also shown that degree of agglomeration, 26,44,45 charge, 46 surface chemical modification, 47 and metal contaminants 48 could affect CNT toxicity in vivo or in vitro. Comparing with f-MWCNT, more inflammation occurred in the p-MWCNTs.…”

Section: Physicochemical Characteristic Dependency Of Effects/relatiomentioning

confidence: 99%

“…With extensive biomedical applications, large variety of surface-modified CNTs should be systematically evaluated in toxic effects in vivo, especially in immunotoxicity. Furthermore, other factors influence the toxicity effects of MWCNTs and have the potential to modulate their biological effects, such as their sizes, 25 lengths, 26 and contamination with metal catalysts. 27 Several data indicate that length is one of the most important determinants for toxicity of CNTs and it is unclear whether the length of MWCNTs affects the outcome of immunotoxicity, which is one of the concerns in our study.…”

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confidence: 99%

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Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

Zhang¹,

Meng²,

Zhang³

et al. 2017

IJN

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The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3 + , CD4 + , CD8 + , and CD19 + ) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs.

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Section: Physicochemical Characteristic Dependency Of Effects/relatiomentioning

confidence: 99%

mentioning

confidence: 99%

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

Zhang¹,

Meng²,

Zhang³

et al. 2017

IJN

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“…While there is much ongoing effort for using CNTs in drug delivery and biomedical applications, it is worth noting that there have been concerns about the toxicity of CNTs and numerous in vitro and in vivo studies have been carried out with conflicting reports 40–48 . However, functionalization with carboxyl group has shown to be an effective way to mitigate MWCNTs toxicity 49–50 .…”

Section: Introductionmentioning

confidence: 99%

Incorporation of functionalized carbon nanotubes into hydrophobic drug crystals for enhancing aqueous dissolution

Chen

Mitra

2019

Colloids and Surfaces B: Biointerfaces

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We present for the first time the direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation. The approach was tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that had very different aqueous solubility. It was observed that the f-CNTs dispersed in the water served as nucleating sites for crystallization and were readily incorporated into the drug particles without altering crystal structure or other properties. The results showed that the hydrophilic f-CNTs dramatically enhanced dissolution rate for both drugs, and the time necessary to reach 80% dissolution (t80) reduced from 67 to 10 with the incorporation of 5.1% f-CNTs in SMZ, and from 66 to 18 min with 4.0% f-CNTs in GF. The enhanced dissolution is attributed to the fact that the hydrophilic f-CNTs served as conduits for bringing in water in close contact with the drug crystals.

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“…Anionic –COOH functionalization reduced epithelial, fibroblast, and macrophage cytotoxicity and inflammasome activation (Sayes et al, 2006), while strong cationic surfaces increased surface reactivity, resulting in strong inflammasome activation and fibrogenic potential (Li et al, 2013b). Other studies, however, found no difference between –COOH and –NH 2 functionalized MWCNT toxicity, since functional group presence caused increased protein binding and agglomeration (Allegri et al, 2016; Coccini et al, 2013). …”

Section: Discussionmentioning

confidence: 91%

“…To discern differences in the ability of various carbon ENMs ability to bind lung surfactant and protein that may impact toxicological response, each carbon ENM was incubated with Survanta lung surfactant in SAGM medium, analyzed by SDS Page gels, and bound protein quantified using previously described methods (Allegri et al, 2016). Stained protein bands on gels were imaged and quantified using FluoroChem SP.…”

Section: Methodsmentioning

confidence: 99%

Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells

et al. 2017

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Functionalized multi-walled carbon nanotube (fMWCNT) development has been intensified to improve their surface activity for numerous applications, and potentially reduce toxic effects. Although MWCNT exposures are associated with lung tumorigenesis in vivo, adverse responses associated with exposure to different fMWCNTs in human lung epithelium are presently unknown. This study hypothesized that different plasma-coating functional groups determine MWCNT neoplastic transformation potential. Using our established model, human primary small airway epithelial cells (pSAECs) were continuously exposed for 8 and 12 weeks at 0.06 µg/cm2 to three-month aged as-prepared-(pMWCNT), carboxylated-(MW-COOH), and aminated-MWCNTs (MW-NHx). Ultrafine carbon black (UFCB) and crocidolite asbestos (ASB) served as particle controls. fMWCNTs were characterized during storage, and exposed cells were assessed for several established cancer cell hallmarks. Characterization analyses conducted at 0 and 2 months of aging detected a loss of surface functional groups over time due to atmospheric oxidation, with MW-NHx possessing less oxygen and greater lung surfactant binding affinity. Following 8 weeks of exposure, all fMWCNT-exposed cells exhibited significant increased proliferation compared to controls at 7 d post-treatment, while UFCB- and ASB-exposed cells did not differ significantly from controls. UFCB, pMWCNT, and MW-COOH exposure stimulated significant transient invasion behavior. Conversely, aged MW-NHx-exposed cells displayed moderate increases in soft agar colony formation and morphological transformation potential, while UFCB cells showed a minimal effect compared to all other treatments. In summary, surface properties of aged fMWCNTs can impact cell transformation events in vitro following continuous, occupationally relevant exposures.

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Toxicity determinants of multi-walled carbon nanotubes: The relationship between functionalization and agglomeration

Abstract: Graphical abstract

Cited by 154 publications

References 69 publications

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

Incorporation of functionalized carbon nanotubes into hydrophobic drug crystals for enhancing aqueous dissolution

Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells

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