title: Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.
abstract: We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl(2)). Three assays were used: (1) the Salmonella/microsome assay with four tester strains, (2) the comet assay and (3) the micronucleus test on CHO cells. The contribution of simulated sunlight was studied in the three assays while oxidative events were only explored in the comet assay in aliquots pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the Salmonella/mutagenicity test whereas CdCl(2) was weakly positive. In the dark, both the QDsN and CdCl(2) similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl(2), but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl(2). The present results clearly point to the genotoxic properties and the risk of long-term adverse effects of such a nanoplatform if used for human anticancer therapy and diagnosis in the future.
authors.affiliation: Laboratoire de Mutagenèse Environnementale, Institut Méditerranéen de Biodiversité et d'Ecologie, Aix-Marseille Université, Marseille cedex, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Aye
authors.forename: Carole
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berque-Bestel
authors.forename: Ahissan
authors.initials: A
authors.lastname: Aime
authors.forename: Benoit P
authors.initials: BP
authors.lastname: Pichon
authors.forename: Yves
authors.initials: Y
authors.lastname: Jammes
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthélémy
authors.forename: Michel
authors.initials: M
authors.lastname: De Méo
mesh_terms: D019256:Cadmium Chloride / Q000633:toxicity; D019187:Cadmium Compounds / Q000633:toxicity*; D004249:DNA Damage; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010713:Phosphatidylcholines; D045663:Quantum Dots; D018036:Selenium Compounds / Q000633:toxicity*; D013440:Sulfides; D014529:Uridine / Q000031:analogs & derivatives; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D009153:Mutagens; C511566:N-(5'-(2',3'-dioleoyl)uridine)-N',N',N'-trimethylammonium; D010713:Phosphatidylcholines; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; C017251:1,2-oleoylphosphatidylcholine; D019256:Cadmium Chloride; C031238:zinc sulfide; D014529:Uridine