title: PdO doping tunes band-gap energy levels as well as oxidative stress responses to a Co₃O₄ p-type semiconductor in cells and the lung.
abstract: We demonstrate through PdO doping that creation of heterojunctions on Co3O4 nanoparticles can quantitatively adjust band-gap and Fermi energy levels to study the impact of metal oxide nanoparticle semiconductor properties on cellular redox homeostasis and hazard potential. Flame spray pyrolysis (FSP) was used to synthesize a nanoparticle library in which the gradual increase in the PdO content (0-8.9%) allowed electron transfer from Co3O4 to PdO to align Fermi energy levels across the heterojunctions. This alignment was accompanied by free hole accumulation at the Co3O4 interface and production of hydroxyl radicals. Interestingly, there was no concomitant superoxide generation, which could reflect the hole dominance of a p-type semiconductor. Although the electron flux across the heterojunctions induced upward band bending, the E(c) levels of the doped particles showed energy overlap with the biological redox potential (BRP). This allows electron capture from the redox couples that maintain the BRP from -4.12 to -4.84 eV, causing disruption of cellular redox homeostasis and induction of oxidative stress. PdO/Co3O4 nanoparticles showed significant increases in cytotoxicity at 25, 50, 100, and 200 μg/mL, which was enhanced incrementally by PdO doping in BEAS-2B and RAW 264.7 cells. Oxidative stress presented as a tiered cellular response involving superoxide generation, glutathione depletion, cytokine production, and cytotoxicity in epithelial and macrophage cell lines. A progressive series of acute pro-inflammatory effects could also be seen in the lungs of animals exposed to incremental PdO-doped particles. All considered, generation of a combinatorial PdO/Co3O4 nanoparticle library with incremental heterojunction density allowed us to demonstrate the integrated role of E(v), E(c), and E(f) levels in the generation of oxidant injury and inflammation by the p-type semiconductor, Co3O4.
authors.affiliation: Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin, China.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Suman
authors.initials: S
authors.lastname: Pokhrel
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.forename: Huan
authors.initials: H
authors.lastname: Meng
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Sijie
authors.initials: S
authors.lastname: Lin
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Chang
authors.forename: Linjiang
authors.initials: L
authors.lastname: Li
authors.forename: Ruibin
authors.initials: R
authors.lastname: Li
authors.forename: Bingbing
authors.initials: B
authors.lastname: Sun
authors.forename: Meiying
authors.initials: M
authors.lastname: Wang
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Liao
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Lutz
authors.initials: L
authors.lastname: Mädler
authors.forename: André E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D000818:Animals; D002460:Cell Line; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D010165:Palladium / Q000737:chemistry / Q000633:toxicity*; D012666:Semiconductors / Q000009:adverse effects*
chemical_list: D003603:Cytotoxins; D010087:Oxides; D003035:Cobalt; D010165:Palladium; C048320:palladium oxide; C060728:cobalt oxide