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Pro-NP™ protect against TiO2 nanoparticle-induced phototoxicity in zebrafish model: exploring potential application for skin care

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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.

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Author information

Author notes

  1. Min-Sik Kim

    Present address: Kemin Industries, Inc, 2100 Maury Street, Des Moines, IA, 50317, USA

  2. Bala Vamsi K. Karuturi

    Present address: Mylan Pharmaceuticals Inc., 781 Chestnut Ridge Road, Morgantown, WV, 26505, USA

Authors and Affiliations

  1. Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 5109 Rennebohm Hall, 777 Highland Ave, Madison, WI, 53705, USA

    Min-Sik Kim & Richard E. Peterson

  2. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    Melinda Stees, Sivakumar Vijayaraghavalu & Vinod Labhasetwar

  3. ProTransit Nanotherapy, LLC, Wittson Hall, University of Nebraska Medical Center, 42nd and Emile Streets, Omaha, NE, 68198, USA

    Bala Vamsi K. Karuturi & Gary L. Madsen

Authors
  1. Min-Sik Kim
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  2. Melinda Stees
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  3. Bala Vamsi K. Karuturi
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  4. Sivakumar Vijayaraghavalu
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  5. Richard E. Peterson
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Contributions

MK conducted the experiments; MS formulated Pro-NP™; MK and BK compiled data and prepared the initial manuscript draft; SV carried out UV absorption of Pro-NP™ and particle size characterization; RP, GM, VL designed and supervised the study; and VL compiled final data and wrote the manuscript with contributions from co-authors. Authors reviewed the manuscript prior to submission.

Corresponding author

Correspondence to Vinod Labhasetwar.

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Conflict of interest

The study was funded by ProTransit Nanotherapy, LLC, Omaha, NE, a start-up company based on patented work done at the University of Nebraska Medical Center. GM and VL are co-founders of ProTransit Nanotherapy and have an equity interest in the company. ProTransit can make Pro-NP™ available to potential investigators under material transfer agreement. Potential conflict of interest matters for VL are managed according to guidelines of the Conflict of Interest committee of Cleveland Clinic.

Ethical statement

The use of zebrafish and maintenance plan were approved by the Research Animal Resources Center of the University of Wisconsin-Madison.

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Kim, MS., Stees, M., Karuturi, B.V.K. et al. Pro-NP™ protect against TiO2 nanoparticle-induced phototoxicity in zebrafish model: exploring potential application for skin care. Drug Deliv. and Transl. Res. 7, 372–382 (2017). https://doi.org/10.1007/s13346-017-0374-7

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