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Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots
Authors:Mélanie Aye  Carole Di Giorgio  Isabelle Berque-Bestel  Ahissan Aime  Benoit P. Pichon  Yves Jammes  Philippe Barthélémy  Michel De Méo
Affiliation:1. Laboratoire de Mutagenèse Environnementale, Institut Méditerranéen de Biodiversité et d’Ecologie, Faculté de Pharmacie, Aix-Marseille Université, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France;2. UMR MD2, Faculté de Médecine, Aix-Marseille Université, 13916 Marseille cedex 20, France;3. Université de Bordeaux and INSERM U869 ChemBioMed, 146 Rue Leo Saignat, Bordeaux cedex F-33076, France;4. IPCMS, 23 rue du Loess, BP 43, 67034 Strasbourg cedex 2, France
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 (CdCl2). 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 CdCl2 was weakly positive. In the dark, both the QDsN and CdCl2 similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl2, but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl2. 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.
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