Abstract
Functionalization has been shown to alter toxicity of multi-walled carbon nanotube (MWCNT) in several studies. This study varied the degree of functionalization (viz., amount of MWCNT surface carboxylation) to define the relationship between the extent of carboxylation and effects in a variety of in vitro cell models and short-term ex vivo/in vivo particle exposures. Studies with vitamin D3 plus phorbol ester transformed THP-1 macrophages demonstrated that functionalization, regardless of amount, corresponded with profoundly decreased NLRP3 inflammasome activation. However, all MWCNT variants were slightly toxic in this model. Alternatively, studies with A549 epithelial cells showed some varied effects. For example, IL-33 and TNF-α release were related to varying amounts of functionalization. For in vivo particle exposures, autophagy of alveolar macrophages, measured using green fluorescent protein (GFP)- fused-LC3 transgenic mice, increased for all MWCNT tested three days after exposure, but, by Day 7, autophagy was clearly dependent on the amount of carboxylation. The instilled source MWCNT continued to produce cellular injury in alveolar macrophages over seven days. In contrast, the more functionalized MWCNT initially showed similar effects, but reduced over time. Dark-field imaging showed the more functionalized MWCNTs were distributed more uniformly throughout the lung and not isolated to macrophages. Taken together, the results indicated that in vitro and in vivo bioactivity of MWCNT decreased with increased carboxylation. Functionalization by carboxylation eliminated the bioactive potential of the MWCNT in the exposure models tested. The observation that maximally functionalized MWCNT distribute more freely throughout the lung with the absence of cellular damage, and extended deposition, may establish a practical use for these particles as a safer alternative for unmodified MWCNT.
Highlights
Multi-walled carbon nanotubes (MWCNTs) are a family of engineered nanomaterials consisting of concentric tubes of graphite with properties that are conducive to mechanical and electrical applications
The morphology of MWCNTs is shown in TEM image (Figure 1A)
The elemental analysis of MWCNTs and f-MWCNTs were measured by EDX (Table 2)
Summary
Multi-walled carbon nanotubes (MWCNTs) are a family of engineered nanomaterials consisting of concentric tubes of graphite with properties that are conducive to mechanical and electrical applications. These materials are currently mass produced and are found in a variety of materials, ranging from composites, storage devices, pharmaceutical drug deliveries, optics, and engineering products [1]. The toxic properties of MWCNTs have been documented in numerous cell and animal exposure models, with particle length and rigidity mimicking asbestos fibers being the properties most commonly associated with harmful interactions [5]. While the exact mechanisms and relevant physicochemical properties remain to be fully defined, there is a clear need to further develop and test modified MWCNTs with better safety profiles
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