Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation

Abstract

We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase. However, whether peroxidase intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals.

Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura

“…There have been suggestions that CNTs can undergo a degree of dissolution depending on their form 42,43 ; thus, the retention/translocation kinetics of long CNTs from the pleural space could change over time if the CNTs undergo any biodissolution. Recently, Tomatis et al 44 reported that the greater toxicity of long asbestos fibers when compared with short asbestos fibers could be attributed to several factors other than length, including greater free radical production and reactive surface.…”

Folate and iron difunctionalized multiwall carbon nanotubes as dual-targeted drug nanocarrier to cancer cells

“…Moreover, it has been discovered that CNTs could be metabolized by neutrophil myeloperoxidase [6] and the functionalized CNTs (f-CNTs) have less cytoxicity [7]. In the past 10 years, a variety of f-CNTs including oxidized, aminated, surfactant-assisted dispersed, polymer-assisted dispersed, and bio-molecular modified CNTs have been discovered [8] and utilized as the effective bio-molecular carriers to deliver peptides, proteins, nucleic acids and small molecular drugs into cellular systems.…”

Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles

“…However, polystyrene has been shown to be resistant to thermal oxidation below 200°C, which is far above the viability limit of in vitro biological conditions. [37][38][39] A high level of lysosomal accumulation was associated with a low level of cytokine signalling 24 h post exposure of the BBB monolayer to 100 nm PS COOH NPs. Inflammasome activation due to lysosome signalling is associated with an increase in activated IL1-beta levels, which were not found in this study.…”