title: PEGylated single-walled carbon nanotubes activate neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes.
abstract: Perspectives for the use of carbon nanotubes in biomedical applications depend largely on their ability to degrade in the body into products that can be easily cleared out. Carboxylated single-walled carbon nanotubes (c-SWCNTs) were shown to be degraded by oxidants generated by peroxidases in the presence of hydrogen peroxide. In the present study we demonstrated that conjugation of poly(ethylene glycol) (PEG) to c-SWCNTs does not interfere with their degradation by peroxidase/H(2)O(2) system or by hypochlorite. Comparison of different heme-containing proteins for their ability to degrade PEG-SWCNTs has led us to conclude that the myeloperoxidase (MPO) product hypochlorous acid (HOCl) is the major oxidant that may be responsible for biodegradation of PEG-SWCNTs in vivo. MPO is secreted mainly by neutrophils upon activation. We hypothesize that SWCNTs may enhance neutrophil activation and therefore stimulate their own biodegradation due to MPO-generated HOCl. PEG-SWCNTs at concentrations similar to those commonly used in in vivo studies were found to activate isolated human neutrophils to produce HOCl. Both PEG-SWCNTs and c-SWCNTs enhanced HOCl generation from isolated neutrophils upon serum-opsonized zymosan stimulation. Both types of nanotubes were also found to activate neutrophils in whole blood samples. Intraperitoneal injection of a low dose of PEG-SWCNTs into mice induced an increase in percentage of circulating neutrophils and activation of neutrophils and macrophages in the peritoneal cavity, suggesting the evolution of an inflammatory response. Activated neutrophils can produce high local concentrations of HOCl, thereby creating the conditions favorable for degradation of the nanotubes.
authors.affiliation: Research Institute for Physico-Chemical Medicine, Federal Medico-Biological Agency, Moscow, Russia. irina.vlasova@yahoo.com
authors.forename: Irina I
authors.initials: II
authors.lastname: Vlasova
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Vakhrusheva
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sokolov
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Kostevich
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Gusev
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Gusev
authors.forename: Viktoriya I
authors.initials: VI
authors.lastname: Melnikova
authors.forename: Anatolii S
authors.initials: AS
authors.lastname: Lobach
mesh_terms: D000818:Animals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D037742:Nanotubes, Carbon / Q000737:chemistry*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010529:Peritoneal Cavity; D009195:Peroxidase / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012973:Sodium Hypochlorite / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D016877:Oxidants; D011092:Polyethylene Glycols; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D012973:Sodium Hypochlorite; D009195:Peroxidase