In vivo and In vitro Toxicity and Anti-Inflammatory Properties of Gold Nanoparticle Bioconjugates to the Vascular System

Autor(es)

Uchiyama, Mayara Klimuk ^[1] ; Deda, Daiana Kotra ^[1] ; de Paula Rodrigues, Stephen Fernandes ^[2] ; Drewes, Carine Cristiane ^[2] ; Bolonheis, Simone Marques ^[2] ; Kiyohara, Pedro Kunihiko ^[3] ; de Toledo, Simone Perche ^[3] ; Colli, Walter ^[4] ; Araki, Koiti ^[1] ; Poliselli Farsky, Sandra Helena ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Phys, Dept Gen Phys, BR-05508090 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGICAL SCIENCES; v. 142, n. 2, p. 497-507, DEC 2014.
• Citações Web of Science: 26

Resumo

Gold nanoparticle (AuNP) bioconjugates have been used as therapeutic and diagnostic tools; however, in vivo biocompatibility and cytotoxicity continue to be two fundamental issues. The effect of AuNPs (20nm) conjugated with antibody {[}immunoglobulin G (IgG)], albumin, protein A, PEG4000, and citrate (cit) were evaluated in vitro 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 in vitro, 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 in vivo 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 in vitro. 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 in vitro. Our in vitro and in vivo experimental approaches highlighted the great potentiality of AuNP bioconjugates for therapeutic and diagnostic applications by parenteral routes. (AU)

• Processo FAPESP: 09/08584-6 - Química e nanotecnologia molecular
• Beneficiário: Henrique Eisi Toma
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/19595-9 - Estudo da eficácia terapêutica de nanocápsulas de indometacina e éster etílico de indometacina: ensaios de microscopia intravital
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Regular