PEGylated single-walled carbon nanotubes activate neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes

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 pr...

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Published in:	Toxicology and applied pharmacology Vol. 264; no. 1; pp. 131 - 142
Main Authors:	Vlasova, Irina I., Vakhrusheva, Tatyana V., Sokolov, Alexey V., Kostevich, Valeria A., Gusev, Alexandr A., Gusev, Sergey A., Melnikova, Viktoriya I., Lobach, Anatolii S.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 01-10-2012 Elsevier
Subjects:	60 APPLIED LIFE SCIENCES Animals BIODEGRADATION Carbon CARBON NANOTUBES Cell activation CONCENTRATION RATIO Evolution HEME Humans HYDROGEN PEROXIDE Hydrogen Peroxide - metabolism Hypochlorite HYPOCHLOROUS ACID Hypochlorous Acid - metabolism IN VIVO INFLAMMATION Inflammation - etiology Inflammation - pathology Injections, Intraperitoneal INTRAPERITONEAL INJECTION Leukocytes (neutrophilic) MACROPHAGES Macrophages - metabolism Male MICE Mice, Inbred CBA Myeloperoxidase nanotubes Nanotubes, Carbon - chemistry Neutrophil Activation - drug effects NEUTROPHILS Neutrophils - drug effects Neutrophils - metabolism Oxidants Oxidants - metabolism OXIDIZERS Peritoneal Cavity Peritoneum Peroxidase Peroxidase - metabolism PEROXIDASES Polyethylene glycol POLYETHYLENE GLYCOLS Polyethylene Glycols - chemistry Sodium Hypochlorite - metabolism ZYMOSAN Hypochlorite Neutrophils Carbon nanotubes Myeloperoxidase LPO Macrophages MPO SOZ
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Summary:	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/H2O2 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. ► Myeloperoxidase (MPO) product hypochlorous acid is able to degrade CNTs. ► PEGylated SWCNTs stimulate isolated neutrophils to produce hypochlorous acid. ► SWCNTs are capable of activating neutrophils in blood samples. ► Activation of neutrophils in blood causes an increase in plasma MPO concentration. ► Intraperitoneal injection of PEG-SWCNTs in mice induces an inflammatory response.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2012.07.027