title: Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity.
abstract: We used well-characterized and positively charged nanoparticles (NP(+)) to investigate the importance of cell culture conditions, specifically the presence of serum and proteins, on NP(+) physicochemical characteristics, and the consequences for their endocytosis and genotoxicity in bronchial epithelial cells (16HBE14o-). NP(+) surface charge was significantly reduced, proportionally to NP(+)/serum and NP(+)/BSA ratios, while NP(+) size was not modified. Microscopy studies showed high endocytosis of NP(+) in 16HBE14o-, and serum/proteins impaired this internalization in a dose-dependent manner. Toxicity studies showed no cytotoxicity, even for very high doses of NP(+). No genotoxicity was observed with classic comet assay while primary oxidative DNA damage was observed when using the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase (FPG). The micronucleus test showed NP(+) genotoxicity only for very high doses that cannot be attained in vivo. The low toxicity of these NP(+) might be explained by their high exocytosis from 16HBE14o- cells. Our results confirm the importance of serum and proteins on nanoparticles endocytosis and genotoxicity.
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France.
authors.forename: Maysaloun
authors.initials: M
authors.lastname: Merhi
authors.forename: Christophe Youta
authors.initials: CY
authors.lastname: Dombu
authors.forename: Alizée
authors.initials: A
authors.lastname: Brient
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Anne
authors.initials: A
authors.lastname: Platel
authors.forename: Frank
authors.initials: F
authors.lastname: Le Curieux
authors.forename: Daniel
authors.initials: D
authors.lastname: Marzin
authors.forename: Fabrice
authors.initials: F
authors.lastname: Nesslany
authors.forename: Didier
authors.initials: D
authors.lastname: Betbeder
mesh_terms: D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D004811:Epichlorohydrin / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D015162:Micronucleus Tests; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D010316:Particle Size; D011134:Polysaccharides / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D055672:Static Electricity
chemical_list: D001798:Blood Proteins; D002412:Cations; D004852:Epoxy Compounds; D011134:Polysaccharides; D000644:Quaternary Ammonium Compounds; D004811:Epichlorohydrin; D012710:Serum Albumin, Bovine; C045006:glycidyl trimethylammonium; C008315:maltodextrin; D043382:DNA-Formamidopyrimidine Glycosylase