title: WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo.
abstract: To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO3/Pt nanoparticles that mimic a leukocyte's functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO3/Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye's anterior chamber, we show that WO3/Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer.
authors.affiliation: Department of Ophthalmology and Visual Sciences, 1000 Wall Street, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Emma L
authors.initials: EL
authors.lastname: Coury
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Meilhac
authors.forename: Howard R
authors.initials: HR
authors.lastname: Petty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D032701:Biomimetics / Q000379:methods; D002384:Catalysis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D017665:Hydroxyl Radical / Q000737:chemistry; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D019255:NADPH Oxidases / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology; D010984:Platinum / Q000494:pharmacology*; D014414:Tungsten / Q000494:pharmacology*
chemical_list: D010087:Oxides; D017319:Photosensitizing Agents; D017665:Hydroxyl Radical; D010984:Platinum; C511604:tungsten oxide; D019255:NADPH Oxidases; D014414:Tungsten