title: Photosensitive fluorescent dye contributes to phototoxicity and inflammatory responses of dye-doped silica NPs in cells and mice.
abstract: Dye-doped fluorescent silica nanoparticles provide highly intense and photostable fluorescence signals. However, some dopant dye molecules are photosensitive. A widely-used photosensitive fluorescent dopant, RuBpy, was chosen to systematically investigate the phototoxicity of the dye-doped silica nanoparticles (NPs). We investigated cell viability, DNA damage, and Reactive Oxygen Species (ROS) levels in alveolar macrophages using the dye-doped NPs with or without irradiation. Our results showed that the RuBpy-doped silica NPs could induce significant amount of ROS, DNA damage, apoptosis and impaired proliferation in MH-S cells. In vivo studies in mice showed that RuBpy-doped silica NPs induced significant inflammatory cytokine production and lowered expression in signaling proteins such as ERK1/2 and NF-κB as well as increased lung injury determined by myeloperoxidase and lipid peroxidation. Strikingly, we also found that both RuBpy alone and NPs induced systemic signaling activation in the kidney compared to the liver and lung where showed highly selective signaling patterns, which is more pronounced than RuBpy-doped silica NPs. Moreover, we discovered a critical biomarker (e.g., HMGB1) for silica NPs-induced stress and toxicity and demonstrated differentially-regulated response patterns in various organs. Our results indicate for the first time that the RuBpy-doped silica NPs may impose less inflammatory responses but stronger thermotherapeutic effects on target cells in animals than naked NPs in a time- and dose-dependent manner.
authors.affiliation: 1. Department of Chemistry, School of Arts and Sciences;
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 2. Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: 2. Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58202, USA.
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1. Department of Chemistry, School of Arts and Sciences;
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1. Department of Chemistry, School of Arts and Sciences;
authors.forename: Yuihui
authors.initials: Y
authors.lastname: Jin
authors.affiliation: 1. Department of Chemistry, School of Arts and Sciences;
authors.forename: Aaron
authors.initials: A
authors.lastname: Hanson
authors.affiliation: 1. Department of Chemistry, School of Arts and Sciences;
authors.forename: Julia Xiaojun
authors.initials: JX
authors.lastname: Zhao
authors.affiliation: 2. Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005456:Fluorescent Dyes / Q000633:toxicity; D024243:HMGB1 Protein / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide; D018675:Toxicity Tests / Q000379:methods
chemical_list: D016207:Cytokines; D005456:Fluorescent Dyes; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C415768:tris(2,2'-bipyridyl)ruthenium(II); D012822:Silicon Dioxide
keywords: 2'-bipyridyl)dichlororuthenium(II) hexahydrate (RuBpy); Silica NPs; fluorescence; phototoxicity; reactive oxygen species.; tris(2