title: Safe-by-Design CuO Nanoparticles via Fe-Doping, Cu-O Bond Length Variation, and Biological Assessment in Cells and Zebrafish Embryos.
abstract: The safe implementation of nanotechnology requires nanomaterial hazard assessment in accordance with the material physicochemical properties that trigger the injury response at the nano/bio interface. Since CuO nanoparticles (NPs) are widely used industrially and their dissolution properties play a major role in hazard potential, we hypothesized that tighter bonding of Cu to Fe by particle doping could constitute a safer-by-design approach through decreased dissolution. Accordingly, we designed a combinatorial library in which CuO was doped with 1-10% Fe in a flame spray pyrolysis reactor. The morphology and structural properties were determined by XRD, BET, Raman spectroscopy, HRTEM, EFTEM, and EELS, which demonstrated a significant reduction in the apical Cu-O bond length while simultaneously increasing the planar bond length (Jahn-Teller distortion). Hazard screening was performed in tissue culture cell lines and zebrafish embryos to discern the change in the hazardous effects of doped vs nondoped particles. This demonstrated that with increased levels of doping there was a progressive decrease in cytotoxicity in BEAS-2B and THP-1 cells, as well as an incremental decrease in the rate of hatching interference in zebrafish embryos. The dissolution profiles were determined and the surface reactions taking place in Holtfreter's solution were validated using cyclic voltammetry measurements to demonstrate that the Cu+/Cu2+and Fe2+/Fe3+redox species play a major role in the dissolution process of pure and Fe-doped CuO. Altogether, a safe-by-design strategy was implemented for the toxic CuO particles via Fe doping and has been demonstrated for their safe use in the environment.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Naatz
authors.affiliation: College of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Tongji University , Shanghai 200092, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: Lin
authors.affiliation: School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Medical College of Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Ruibin
authors.identifier: 0000-0001-6471-7658
authors.initials: R
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Chang
authors.forename: Jan
authors.initials: J
authors.lastname: Köser
authors.forename: Jorg
authors.initials: J
authors.lastname: Thöming
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
authors.forename: Lutz
authors.initials: L
authors.lastname: Mädler
authors.forename: Suman
authors.identifier: 0000-0001-5712-2824
authors.initials: S
authors.lastname: Pokhrel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D000074084:THP-1 Cells; D015027:Zebrafish / Q000196:embryology
chemical_list: D003300:Copper; D007501:Iron; D010100:Oxygen; C030973:cupric oxide
keywords: CuO nanoparticles; Fe doping; Jahn−Teller distortion; cyclic voltammetry; flame spray pyrolysis; safe-by-design