Photosensitive Fluorescent Dye Contributes to Phototoxicity and Inflammatory Responses of Dye-doped Silica NPs in Cells and Mice

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.