title: ABC transporters affect the elimination and toxicity of CdTe quantum dots in liver and kidney cells.
abstract: This paper aimed to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters on the efflux and the toxicity of nanoparticles in liver and kidney cells. In this study, we synthesized CdTe quantum dots (QDs) that were monodispersed and emitted green fluorescence (maximum peak at 530nm). Such QDs tended to accumulate in human hepatocellular carcinoma cells (HepG2), human kidney cells 2 (HK-2), and Madin-Darby canine kidney (MDCK) cells, and cause significant toxicity in all the three cell lines. Using specific inhibitors and inducers of P-glycoprotein (Pgp) and multidrug resistance associated proteins (Mrps), the cellular accumulation and subsequent toxicity of QDs in HepG2 and HK-2 cells were significantly affected, while only slight changes appeared in MDCK cells, corresponding well with the functional expressions of ABC transporters in cells. Moreover, treatment of QDs caused concentration- and time- dependent induction of ABC transporters in HepG2 and HK-2 cells, but such phenomenon was barely found in MDCK cells. Furthermore, the effects of CdTe QDs on ABC transporters were found to be greater than those of CdCl2 at equivalent concentrations of cadmium, indicating that the effects of QDs should be a combination of free Cd(2+) and specific properties of QDs. Overall, these results indicated a strong dependence between the functional expressions of ABC transporters and the efflux of QDs, which could be an important reason for the modulation of QDs toxicity by ABC transporters.
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Chen
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China.
authors.forename: Huancai
authors.initials: H
authors.lastname: Yin
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China.
authors.forename: Pengli
authors.initials: P
authors.lastname: Bai
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Miao
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, Ontario, L8S 4L7, Canada.
authors.forename: Xudong
authors.initials: X
authors.lastname: Deng
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China. Electronic address: yinj@sibet.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019187:Cadmium Compounds / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004285:Dogs; D056945:Hep G2 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D061985:Madin Darby Canine Kidney Cells; D009842:Oligopeptides / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D045663:Quantum Dots / Q000633:toxicity*; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D013691:Tellurium / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D018528:ATP-Binding Cassette Transporters; D019187:Cadmium Compounds; D009842:Oligopeptides; D011422:Propionates; D011804:Quinolines; D012333:RNA, Messenger; C120261:reversin 205; C059141:verlukast; D016572:Cyclosporine; D013691:Tellurium; D011339:Probenecid; C028337:cadmium telluride; D012293:Rifampin
keywords: Kidney cells; Liver cells; Multi-resistance associated proteins; P-glycoprotein; Quantum dot elimination