title: H2O2-Depleting and O2-Generating Selenium Nanoparticles for Fluorescence Imaging and Photodynamic Treatment of Proinflammatory-Activated Macrophages.
abstract: Macrophages have a pivotal role in chronic inflammatory diseases (CIDs), so imaging and controlling activated macrophage is critical for detecting and reducing chronic inflammation. In this study, photodynamic selenium nanoparticles (SeNPs) with photosensitive and macrophage-targeting bilayers were developed. The first layer of the photosensitive macromolecule was composed of a conjugate of a photosensitizer (rose bengal, RB) and a thiolated chitosan (chitosan-glutathione), resulting in a plasmonic coupling-induced red shift and broadening of RB absorption bands with increased absorption intensity. Electron paramagnetic resonance (EPR) and diphenylanthracene (DPA) quenching studies revealed that the SeNPs that were coated with the photosensitive layer were more effective than RB alone in producing singlet oxygen (1O2) under photoirradiation. The second layer of the activated macrophage-targetable macromolecule was synthesized by conjugation of hyaluronic acid with folic acid using an ethylenediamine linker. Proinflammatory-activated macrophages rapidly internalized the SeNPs that were covered with the targeting ligand, exhibiting a much stronger fluorescence signal of the SeNPs than did the nonactivated macrophages. Since proinflammatory-activated macrophage was known to generate a substantial amount of H2O2while the inflamed site generally caused inflammation-associated tissue hypoxia, the SeNPs were further modified with O2self-sufficient function for photodynamic therapy. Catalase was immobilized on the SeNPs by the formation of disulfide bonds. Intracellular reduction of disulfide bonds induced the subsequent release of catalase, which catalyzed the decomposition of H2O2. The H2O2-depleting and O2-generating photodynamic SeNPs efficiently killed activated macrophages and quenched the intracellular H2O2and NO that are associated with inflammation. The SeNPs may have potential as a theranostic nanomaterial to image and control the activation of macrophages.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Kun-Ying
authors.initials: KY
authors.lastname: Lu
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University , Hsinchu 30013, Taiwan.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Er-Yuan
authors.identifier: http://orcid.org/0000-0002-1593-4573
authors.initials: EY
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.|Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Chwen-Ming
authors.initials: CM
authors.lastname: Shih
authors.affiliation: Graduate Institute of Translational Medicine, College of Medicine and Technology, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Tsai-Mu
authors.initials: TM
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Tsung-Yao
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University , Hsinchu 30013, Taiwan.|Institute of Biomedical Engineering, National Tsing Hua University , Hsinchu 30013, Taiwan, ROC.
authors.forename: Hsing-Wen
authors.identifier: http://orcid.org/0000-0002-0789-5236
authors.initials: HW
authors.lastname: Sung
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.|Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.|Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Fwu-Long
authors.identifier: http://orcid.org/0000-0001-8063-3358
authors.initials: FL
authors.lastname: Mi
mesh_terms: D005453:Fluorescence; D006861:Hydrogen Peroxide; D008264:Macrophages; D053758:Nanoparticles; D010100:Oxygen; D012643:Selenium
chemical_list: D006861:Hydrogen Peroxide; D012643:Selenium; D010100:Oxygen
keywords: Se nanoparticles; fluorescence imaging; macrophage; photodynamics