期刊
TOXICOLOGY IN VITRO
卷 29, 期 5, 页码 819-827出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2015.02.010
关键词
Gold nanoparticle; PEG; Nanotoxicity; Bioengineering; Skeletal muscle; Inflammation
类别
资金
- FAPERJ (Fundacao de Amparo a Pesquisa do Rio de Janeiro)
- CNPQ (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- FINEP (Financiadora de Estudos e Projetos)
- PRONAMETRO (Programa de Apoio ao Desenvolvimento da Metrologia, Qualidade e Tecnologia) of INMETRO
- European Union's Seventh Programme for research, technological development and demonstration (NanoValid) [263147]
Gold nanoparticles (AuNP) have been widely used for many applications, including as biological carriers. A better understanding concerning AuNP safety on muscle cells is crucial, since it could be a potential tool in the nanomedicine field. Here, we describe the impact of polyethylene glycol-coated gold nanoparticles (PEG-AuNP) interaction with differentiated skeletal muscle C2C12 cells on cell viability, mitochondria function, cell signaling related to survival, cytokine levels and susceptibility to apoptosis. Intracellular localization of 45 nm PEG-AuNP diameter size was evidenced by STEM-in-SEM in myotube cells. Methods for cytotoxicity analysis showed that PEG-AuNP did not affect cell viability, but intracellular ATP levels and mitochondrial membrane potential increased. Phosphorylation of ERK was not altered but p-AKT levels reduced (p < 0.01). Pre-treatment of cells with PEG-AuNP followed by staurosporine induction increased the caspases-3/7 activity. Indeed, cytokines analysis revealed a sharp increase of IFN-gamma and TGF-beta 1 levels after PEG-AuNP treatment, suggesting that inflammatory and fibrotic phenotypes process were activated. These data demonstrate that PEG-AuNP affect the myotube physiology leading these cells to be more susceptible to death stimuli in the presence of staurosporine. Altogether, these results present evidence that PEG-AuNP affect the susceptibility to apoptosis of muscle cells, contributing to development of safer strategies for intramuscular delivery. (C) 2015 Elsevier Ltd. All rights reserved.
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