title: Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses.
abstract: Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFβ signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles.
authors.affiliation: Institute of Labor, Occupational Safety and Health, Ministry of Labor, Taipei Medical University Hospital, Taipei, Taiwan ; School of Public Health, National Defense Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chih-Hong
authors.initials: CH
authors.lastname: Pan
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University Hospital, Taipei, Taiwan ; School of Respiratory Therapy, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Wen-Te
authors.initials: WT
authors.lastname: Liu
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan ; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Mauo-Ying
authors.initials: MY
authors.lastname: Bien
authors.affiliation: Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: I-Chan
authors.initials: IC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Environmental Engineering, National Central University, Taoyuan, Taiwan.
authors.forename: Ta-Chih
authors.initials: TC
authors.lastname: Hsiao
authors.affiliation: Department of Cosmetic Application and Management, St Mary's Junior College of Medicine, Nursing and Management, Sanxing, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ma
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Ching-Huang
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Mei-Chieh
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kai-Jen
authors.initials: KJ
authors.lastname: Chuang
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University Hospital, Taipei, Taiwan ; School of Respiratory Therapy, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Chuang
mesh_terms: D000537:Aluminum Oxide / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000145:classification; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000187:drug effects*; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity
chemical_list: D011506:Proteins; D020543:Proteome; D000537:Aluminum Oxide; D015034:Zinc Oxide
keywords: WNT pathway; aluminium-doped zinc oxide; nanoparticle; pH; toxicology; zeta potential