title: Photodynamic N-TiO2Nanoparticle Treatment Induces Controlled ROS-mediated Autophagy and Terminal Differentiation of Leukemia Cells.
abstract: In this study, we used nitrogen-doped titanium dioxide (N-TiO2) NPs in conjugation with visible light, and show that both reactive oxygen species (ROS) and autophagy are induced by this novel NP-based photodynamic therapy (PDT) system. While well-dispersed N-TiO2NPs (≤100 μg/ml) were inert, their photo-activation with visible light led to ROS-mediated autophagy in leukemia K562 cells and normal peripheral lymphocytes, and this increased in parallel with increasing NP concentrations and light doses. At a constant light energy (12 J/cm2), increasing N-TiO2NP concentrations increased ROS levels to trigger autophagy-dependent megakaryocytic terminal differentiation in K562 cells. By contrast, an ROS challenge induced by high N-TiO2NP concentrations led to autophagy-associated apoptotic cell death. Using chemical autophagy inhibitors (3-methyladenine and Bafilomycin A1), we confirmed that autophagy is required for both terminal differentiation and apoptosis induced by photo-activated N-TiO2. Pre-incubation of leukemic cells with ROS scavengers muted the effect of N-TiO2NP-based PDT on cell fate, highlighting the upstream role of ROS in our system. In summary, PDT using N-TiO2NPs provides an effective method of priming autophagy by ROS induction. The capability of photo-activated N-TiO2NPs in obtaining desirable cellular outcomes represents a novel therapeutic strategy of cancer cells.
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Moosavi
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.|Cell and Molecular Biology Department, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sharifi
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Science, Tabriz, Iran.|Department of Nanobiotechnology, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran.
authors.forename: Soroush Moasses
authors.initials: SM
authors.lastname: Ghafary
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mohammadalipour
authors.affiliation: Research Laboratory of Advanced Water and Wastewater Treatment Processes, Department of Applied Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.|Department of Materials Science and Nanotechnology, Near East University, 99138 Nicosia, North Cyprus, Mersin 10, Turkey.
authors.forename: Alireza
authors.initials: A
authors.lastname: Khataee
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marveh
authors.initials: M
authors.lastname: Rahmati
authors.affiliation: Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Hajjaran
authors.affiliation: LinkoCare Life Sciences AB, 583 30 Linköping, Sweden; Malopolska Centre of Biotechnology Jagiellonian University Gronostajowa 7A str 30-387 Krakow, Poland.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Łos
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.|Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada.|Health Research Policy Centre, Shiraz University of Medical Science, Shiraz, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009584:Nitrogen / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D009584:Nitrogen