title: Pro-NP™ protect against TiO2 nanoparticle-induced phototoxicity in zebrafish model: exploring potential application for skin care.
abstract: Titanium dioxide nanoparticles (TiO2NPs) are used in sunscreen products to protect the skin from the sun's ultraviolet rays. However, following exposure to sunlight, the photocatalytic activity of TiO2NPs can produce an excess of reactive oxygen species (ROS), causing skin cell damage, triggering an inflammatory response. In zebrafish model, we evaluated how well Pro-NP™ (biodegradable NPs containing superoxide dismutase and catalase) could protect them from TiO2NP-induced photo-oxidative stress. We hypothesized that the antioxidant properties of Pro-NP™ would protect zebrafish embryos from the phototoxic effects of TiO2NPs, improving overall survival and growth. Dechorionated embryos were treated with TiO2NPs alone or co-treated with Pro-NP™, and then exposed to simulated sunlight. Pro-NP™ by itself caused no toxicity; however, for embryos exposed to 100 μg/ml TiO2NPs, zebrafish survival was reduced to ∼40% and at 500 μg/ml to ∼10%. In contrast, at 100 μg/ml TiO2NP, co-treatment with Pro-NP™ increased zebrafish survival in a dose-dependent manner. Co-treatment also improved percent of embryos hatching and resulted in normal growth of zebrafish. On the other hand, embryos treated with TiO2NPs alone developed deformities, had reduced pigmentation, and showed severely truncated growth. Pro-NP™ afforded a greater level of protection against TiO2NP-induced phototoxicity than other antioxidants (vitamin E or N-acetylcysteine) commonly used in topical skin care formulations. We conclude that Pro-NP™ exert significant protective effects against TiO2NP-induced phototoxicity and could be developed as a safe, effective skin care product, used alone or in combination with sunscreen products to protect the skin from sun's UV radiation.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 5109 Rennebohm Hall, 777 Highland Ave, Madison, WI, 53705, USA.|Kemin Industries, Inc, 2100 Maury Street, Des Moines, IA, 50317, USA.
authors.forename: Min-Sik
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Stees
authors.affiliation: ProTransit Nanotherapy, LLC, Wittson Hall, University of Nebraska Medical Center, 42nd and Emile Streets, Omaha, NE, 68198, USA.|Mylan Pharmaceuticals Inc., 781 Chestnut Ridge Road, Morgantown, WV, 26505, USA.
authors.forename: Bala Vamsi K
authors.initials: BVK
authors.lastname: Karuturi
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Vijayaraghavalu
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 5109 Rennebohm Hall, 777 Highland Ave, Madison, WI, 53705, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Peterson
authors.affiliation: ProTransit Nanotherapy, LLC, Wittson Hall, University of Nebraska Medical Center, 42nd and Emile Streets, Omaha, NE, 68198, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Madsen
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. labhasv@ccf.org.
authors.forename: Vinod
authors.initials: V
authors.lastname: Labhasetwar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects; D005260:Female; D008297:Male; D053758:Nanoparticles / Q000528:radiation effects / Q000633:toxicity*; D013472:Sunlight / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014025:Titanium / Q000528:radiation effects / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D000975:Antioxidants; C009495:titanium dioxide; D014025:Titanium; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Antioxidants; Nanoparticles; Oxidative stress; Reactive oxygen species; Skin damage; Ultraviolet rays