title: Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death.
abstract: 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 4.5 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-γ and TGF-β1 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.
authors: Divisão de Biologia Celular e Bioengenharia, Diretoria de Metrologia Aplicada as Ciências da Vida (DIMAV), Brazil. Electronic address: leitepec@gmail.com.
authors: Paulo Emílio Corrêa
authors: PE
authors: Leite
authors: Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors: Mariana Rodrigues
authors: MR
authors: Pereira
authors: Divisão de Biologia Celular e Bioengenharia, Diretoria de Metrologia Aplicada as Ciências da Vida (DIMAV), Brazil.
authors: Carlos Antonio
authors: CA
authors: do Nascimento Santos
authors: Divisão de Metrologia de Materiais (DIMAT), Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), 25250-020 Duque de Caxias, RJ, Brazil.
authors: Andrea Porto Carreiro
authors: AP
authors: Campos
authors: Divisão de Biologia Celular e Bioengenharia, Diretoria de Metrologia Aplicada as Ciências da Vida (DIMAV), Brazil.
authors: Ticiana Mota
authors: TM
authors: Esteves
authors: Divisão de Biologia Celular e Bioengenharia, Diretoria de Metrologia Aplicada as Ciências da Vida (DIMAV), Brazil; Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors: José Mauro
authors: JM
authors: Granjeiro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D007371:Interferon-gamma / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D011092:Polyethylene Glycols; D006046:Gold; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7
keywords: Bioengineering; Gold nanoparticle; Inflammation; Nanotoxicity; PEG; Skeletal muscle