title: In vitro toxicity assessment of amphiphillic polymer-coated CdSe/ZnS quantum dots in two human liver cell models.
abstract: Semiconductor quantum dots (Qdots) are a promising new technology with benefits in the areas of medical diagnostics and therapeutics. Qdots generally consist of a semiconductor core, capping shell, and surface coating. The semiconductor core of Qdots is often composed of group II and VI metals (e.g., Cd, Se, Te, Hg) that are known to have toxic properties. Various surface coatings have been shown to stabilize Qdots and thus shield cells from the toxic properties of their core elements. In this study, HepG2 cells and primary human liver (PHL) cells were chosen as in vitro tissue culture models of human liver to examine the possible adverse effects of tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) copolymer (TOPO-PMAT)-coated CdSe/ZnS Qdots (TOPO-PMAT Qdots). The TOPO-PMAT coating is desirable for increasing aqueous solubility and ease of conjugation to targeting moieties (e.g., aptamers and peptides). HepG2 cells avidly incorporated these TOPO-PMAT Qdots into subcellular vesicles. However, PHL cells did not efficiently take up TOPO-PMAT Qdots, but nonparenchymal cells did (especially Kupffer cells). No acute toxicity or morphological changes were noted in either system at the exposure levels used (up to 40 nM). However, cellular stress markers and pro-inflammatory cytokines/chemokines were increased in the PHL cell cultures, suggesting that TOPO-PMAT Qdots are not likely to cause acute cytotoxicity in the liver but may elicit inflammation/hepatitis, demonstrating the importance of relevant preclinical safety models. Thus, further in vivo studies are warranted to ensure that TOPO-PMAT-coated Qdots used in biomedical applications do not induce inflammatory responses as a consequence of hepatic uptake.
authors.affiliation: Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington 98195, United States.
authors.forename: Wesley E
authors.initials: WE
authors.lastname: Smith
authors.forename: Jessica
authors.initials: J
authors.lastname: Brownell
authors.forename: Collin C
authors.initials: CC
authors.lastname: White
authors.forename: Zahra
authors.initials: Z
authors.lastname: Afsharinejad
authors.forename: Jesse
authors.initials: J
authors.lastname: Tsai
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Hu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Polyak
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Gao
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Kavanagh
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
mesh_terms: D019187:Cadmium Compounds / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000633:toxicity*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009943:Organophosphorus Compounds / Q000633:toxicity; D011108:Polymers / Q000633:toxicity*; D045663:Quantum Dots; D018036:Selenium Compounds / Q000633:toxicity*; D013440:Sulfides / Q000633:toxicity*; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D020099:Coated Materials, Biocompatible; D009943:Organophosphorus Compounds; D011108:Polymers; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C512883:poly(1-tetradecene-alt-maleic acid); C044965:trioctyl phosphine oxide; C058667:cadmium selenide; C031238:zinc sulfide