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Toxicological sciences : an official journal of the Society of Toxicology

In vivo and in vitro toxicity and anti-inflammatory properties of gold nanoparticle bioconjugates to the vascular system.


PMID 25260831

Abstract

Gold nanoparticle (AuNP) bioconjugates have been used as therapeutic and diagnostic tools; however, inxa0vivo biocompatibility and cytotoxicity continue to be two fundamental issues. The effect of AuNPs (20 nm) conjugated with antibody [immunoglobulin G (IgG)], albumin, protein A, PEG4000, and citrate (cit) were evaluated inxa0vitro using primary human cells of the vascular system. AuNP bioconjugates did not cause lysis of human erythrocytes, apoptosis or necrosis of human leukocytes, and endothelial cells inxa0vitro, although AuNPs had been internalized and detected in the cytoplasm. Moreover, the influence of AuNPs on rheological parameters, blood and vessel wall characteristics was investigated inxa0vivo by intravital microscopy assay using male Wistar rats mesentery microcirculation as model. Intravenous injection of AuNP-IgG or cit-AuNP did not cause hemorrhage, hemolysis or thrombus formation, instead suppressed the leukocyte adhesion to postcapillary vessel walls, an early stage of an inflammatory process. Furthermore, AuNP-IgG abrogated the expression of platelet-endothelial cell adhesion molecule-1, chemotaxis, and oxidative burst activation on neutrophils after leukotriene B4 stimulation, a membrane receptor-dependent stimulus, thus confirming their anti-inflammatory effects inxa0vitro. The expression of oxidative burst activation was also suppressed after stimulating AuNP-IgG-treated neutrophils with lipid-soluble phorbol myristate acetate (PMA), confirming the direct intracellular action of AuNP-IgG on the inflammatory process inxa0vitro. Our inxa0vitro and inxa0vivo experimental approaches highlighted the great potentiality of AuNP bioconjugates for therapeutic and diagnostic applications by parenteral routes.