Acute in vitro and in vivo toxicity of a commercial grade boron nitride nanotube mixture

Abstract

Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of ∼50-60% BNNTs, and ∼40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 µg/ml and C57BL/6 J male mice were treated with 40 µg of BNNT-M for in vitro and in vivo studies, respectively. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1β and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein production when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The observed results demonstrated acute inflammation and toxicity in vitro and in vivo following exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation.

Preliminary study on conjugation of formononetin with multiwalled carbon nanotubes for inducing apoptosis via ROS production in HeLa cells

“…The high membrane potential could promote JC-1 aggregated in matrix to present red fluorescence, while low potential prevented from aggregation and present green fluorescence. 38 As shown in Figure 10Aa , 3T3 cells exhibited strong red fluorescence in the control, and the FMN ( Figure 10Ab ) and MWCNT-FMN ( Figure 10Ac ) exhibited similar phenomenon compared with the blank control. Figure 10Ba shows that HeLa cells exhibited strong red fluorescence in the control; by contrast, HeLa cells mainly emitted green fluorescence after the cells were exposed to CCCP (carbonyl cyanide m-chlorophenyl hydrazone, positive control) ( Figure 10Bb ), FMN, and MWCNT-FMN.…”

Pulmonary toxicity and lung tumorigenic potential of surrogate metal oxides in gas metal arc welding–stainless steel fume: Iron as a primary mediator versus chromium and nickel

“…To study the impact of the metal oxides on innate immune function, alveolar macrophages from the BAL cell pellet at 1, 7, and 28 days post-exposure to sham, GMAW-SS, or the metal oxides were challenged with Escherichia coli ( E . coli ) GFP for 2 hours at 1:25 MOI (multiplicity of infection) as previously described [25]. The uptake of E .…”

How macrophages respond to two-dimensional materials: a critical overview focusing on toxicity

“…8). [186] In peritoneal macrophages from BALB/c mice, boron induces lymphocyte proliferation and further stimulated secretion of TNF-α, IL-6, IL-1β, NO and expression of iNOS. [187] Pectin-coated boron nitride nanotubes were reported to be non-toxic in RAW 264.7 macrophages at concentrations up to 50 µg/mL for 24 h and were internalized without impairing cell structures or triggering release of inflammatory cytokines (IL-6, IL-10, TNF-α), apoptosis and oxidative stress.…”