Influence of the surface charge of PLGA nanoparticles on their in vitro genotoxicity, cytotoxicity, ROS production and endocytosis.
With the ongoing commercialization of nanotechnology products, human exposure to nanoparticles (NPs) is set to increase dramatically and an evaluation of their potential adverse effects is essential. Surface charge, among other physico-chemicals parameters, is a key criterion that should be considered when using a definition for nanomaterials in a regulatory context. It has recently been recognized as an important factor in determining the toxicity of NPs; however, a complete understanding of the mechanisms involved is still lacking. In this context, the aim of the present study was to investigate the influence of the surface charge modification of NPs on in vitro toxicity assays. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles bearing different surface charges, positive(+), neutral(n) or negative(-), were synthesized. In vitro genotoxicity assays (micronucleus and comet assays) coupled with an assessment of cytotoxicity, were performed in different cell lines (L5178Y mouse lymphoma cells, TK6 human B-lymphoblastoid cells and 16HBE14o- human bronchial epithelial cells). Reactive oxygen species (ROS) production and endocytosis studies were also performed. Our results showed that PLGA(+) NPs were cytotoxic. They are endocytosed by the clathrin pathway and induced ROS in the three cell lines. They led to chromosomal aberrations without primary DNA damage in 16HBE14o- cells, suggesting that aneuploidy may be considered as an important biomarker when assessing the genotoxic potential of NPs. Moreover, 16HBE14o- cells seem to be more suitable for the in vitro screening of inhaled NPs than the regulatory L5178Y and TK6 cells.
Université de Lille 2, 59000, Lille, France.|Institut Pasteur de Lille, Laboratoire de Toxicologie Génétique, 1 rue du Professeur Calmette, BP 245, 59019, Lille, France.|EA4483, Université Lille 2, Faculté de Médecine Pôle Recherche, 1 Place de Verdun, 59045, Lille, France.
Anne
A
Platel
CHRU de Lille, Inserm U995-LIRIC, 59000, Lille, France.|Université d'Artois, 62300, Lens, France.
Rodolphe
R
Carpentier
Université de Lille 2, 59000, Lille, France.|Institut Pasteur de Lille, Laboratoire de Toxicologie Génétique, 1 rue du Professeur Calmette, BP 245, 59019, Lille, France.
Elodie
E
Becart
Université de Lille 2, 59000, Lille, France.|Institut Pasteur de Lille, Laboratoire de Toxicologie Génétique, 1 rue du Professeur Calmette, BP 245, 59019, Lille, France.
Gwendoline
G
Mordacq
Université de Lille 2, 59000, Lille, France.|CHRU de Lille, Inserm U995-LIRIC, 59000, Lille, France.|Université d'Artois, 62300, Lens, France.
Didier
D
Betbeder
Université de Lille 2, 59000, Lille, France.|Institut Pasteur de Lille, Laboratoire de Toxicologie Génétique, 1 rue du Professeur Calmette, BP 245, 59019, Lille, France.|EA4483, Université Lille 2, Faculté de Médecine Pôle Recherche, 1 Place de Verdun, 59045, Lille, France.
Fabrice
F
Nesslany
D000782:Aneuploidy; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002966:Clathrin / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018570:Risk Assessment; D013499:Surface Properties
D002966:Clathrin; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
16HBE14o- human bronchial epithelial cells; L5178Y mouse lymphoma cells; ROS; TK6 human lymphoblastoid cells; endocytosis; genotoxicity, cytotoxicity; nanoparticles of PLGA