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Photodynamic N-TiO 2 Nanoparticle Treatment Induces Controlled ROS-mediated Autophagy and Terminal Differentiation of Leukemia Cells.
- Source :
-
Scientific reports [Sci Rep] 2016 Oct 04; Vol. 6, pp. 34413. Date of Electronic Publication: 2016 Oct 04. - Publication Year :
- 2016
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Abstract
- In this study, we used nitrogen-doped titanium dioxide (N-TiO <subscript>2</subscript> ) 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-TiO <subscript>2</subscript> NPs (≤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/cm <superscript>2</superscript> ), increasing N-TiO <subscript>2</subscript> NP concentrations increased ROS levels to trigger autophagy-dependent megakaryocytic terminal differentiation in K562 cells. By contrast, an ROS challenge induced by high N-TiO <subscript>2</subscript> NP 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-TiO <subscript>2</subscript> . Pre-incubation of leukemic cells with ROS scavengers muted the effect of N-TiO <subscript>2</subscript> NP-based PDT on cell fate, highlighting the upstream role of ROS in our system. In summary, PDT using N-TiO <subscript>2</subscript> NPs provides an effective method of priming autophagy by ROS induction. The capability of photo-activated N-TiO <subscript>2</subscript> NPs in obtaining desirable cellular outcomes represents a novel therapeutic strategy of cancer cells.
- Subjects :
- Humans
K562 Cells
Leukemia metabolism
Leukemia pathology
Autophagy drug effects
Cell Differentiation drug effects
Leukemia drug therapy
Nanoparticles chemistry
Nanoparticles therapeutic use
Nitrogen chemistry
Nitrogen pharmacology
Photochemotherapy methods
Reactive Oxygen Species metabolism
Titanium chemistry
Titanium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27698385
- Full Text :
- https://doi.org/10.1038/srep34413