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Article Cite This: ACS Omega 2019, 4, 1801−1809
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Preparation of Zinc Oxide Nanoparticles Containing Spray and Barrier Films for Potential Photoprotection on Wound Healing Cheng-Chih Lin,† Mei-Hwa Lee,*,‡ Ming-Hong Chi,§ Chen-Jui Chen,‡ and Hung-Yin Lin*,§ †
ACS Omega 2019.4:1801-1809. Downloaded from pubs.acs.org by 146.185.205.234 on 01/24/19. For personal use only.
Division of Pulmonary Medicine, Department of Internal Medicine, Armed Forces Zuoying General Hospital, Kaohsiung 813, Taiwan ‡ Department of Materials Science and Engineering, I-Shou University, Kaohsiung 84001, Taiwan § Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung 81148, Taiwan ABSTRACT: Cutaneous wound healing produces pigmented scars, especially under UV irradiation. In this work, zinc oxide nanoparticles (ZnO NPs) have several morphologies, including nanorods, nanoflowers, and nanospheres. Their size and specific surface area were measured by scanning electron microscopy (SEM) and surface area analysis. The ability of both the ZnO NPs and blends thereof with polymers to protect against phototoxicity was measured using human fibroblast Hs68 cells. Finally, the relative gene expressions of the cellular apoptosis pathway, including p53, Bcl-2, Bax, and Capase 3, were determined by quantitative real-time polymerase chain reaction (qRT-PCR).
1. INTRODUCTION Photoprotection is important in the prevention of photocarcinogenesis, photoaging, and photosensitivity that may otherwise be caused by exposure to the sun.1 The ultraviolet spectrum of solar radiation is arbitrarily divided into three ranges, which are short wave (UVC, 200−280 nm), mid-wave (UVB, 280−320 nm), and long wave (UVA, 320−400 nm).2,3 Most UVC is filtered by the ozone layer in the stratosphere. However, UVB causes acute erythema (peaking after 8−24 h), edema, pigment darkening, delayed tanning, thickening of the epidermis and dermis, and the synthesis of vitamin D, whereas UVA causes immediate pigment darkening (which disappears within 2 h).1 Both UVB and UBA have chronic effects such as photocarcinogenesis, immunosuppression, and photoaging.1 Reducing exposure to ultraviolet radiation and the use of sunscreen are effective methods for preventing the formation of melanoma and the onset of squamous cell skin cancer.3,4 Many biomedical applications of nanoparticles (NPs) have been studied. The optical properties of NPs and the effects of their sizes and shapes are important in bioimaging/biosensing5 and drug delivery/carriers, respectively.6 However, the cytotoxicity of NPs must still be intensively investigated before they can be administered for any of these proposes,7 because the effects of the composition, size, and shape of NPs on their toxicity are still poorly understood. The surface of NPs is usually modified to reduce protein adhesion and subsequent recognition by the immune system.6,8 The complexity of the biological effects of NPs lies in the fact that they are determined not only by their properties but also by their interactions with biomolecules, examples of which include adhesion of biomolecules on NPs and their effects on biological catalysts.6,9 © 2019 American Chemical Society
The skin inflammatory response causes melanocyte migration in the very early stages of wound healing.10−12 Ultraviolet light may cause inflammation (sunburn), redness, and itching of the skin.12 Therefore, exposure to UV or irradiation by the sun should be avoided during skin wound repair.10 DNA damage stabilizes the tumor suppressor protein p53, which activates transcription and increases the expression of the gene-encoding proopiomelanocortin.13 Zinc oxide (ZnO) is an additive in numerous materials and products, including ceramics,14 plastics,15 pigments,16 ointments,17 sealants,18 and food packaging.19 At the beginning of the 20th century, petrolatum and vegetable oils were combined with zinc oxide, magnesium salts, and/or bismuth to protect the skin against the sun.3 The application of zinc oxide to the nose is a common practice. Microfine zinc oxide is a better UV blocker than titanium dioxide,20 but both are somewhat photosensitive and can react with light, inhibiting their efficiency or even causing tissue damage.21,22 Micropigment oxides have to be coated and kept in dispersion,23 which is still a major challenge for the cosmetics industry.1 Published evidence indicates that, as used in cosmetic products23 including sunscreens, micro- and nanosized ZnO and TiO2 do not pose a risk to humans,22,24−26 but dimethicone or silica is generally used to cage these NPs27,28 to reduce the production of reactive oxygen species (ROS).22,29 Recently, different morphologies of ZnO (such as NPs, nanosheets, and nanoflowers) in the form of thin-film photodetectors were demonstrated to have different photoReceived: September 9, 2018 Accepted: December 19, 2018 Published: January 22, 2019 1801
DOI: 10.1021/acsomega.8b02321 ACS Omega 2019, 4, 1801−1809
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Article
Figure 1. SEM images of (a) pencil-like, (b) flower-like, and (c) spherical ZnO NPs in the magnification of 1000× (left) and 10000× (right).
detection capabilities.30 Sheet-like cellulose nanocrystal−ZnO nanohybrid has been introduced into biopolyester as a UV absorber and antibacterial agents.31 ZnO-containing wound dressings, in which zinc oxide and turmeric extract are combined as an anti-inflammatory, were developed.32 The antimicrobial effects of inorganic NPs in combination with the use of collagen promote wound healing.33 Zinc confers resistance to epithelial apoptosis through cytoprotection against ROS and bacterial toxins possibly because of the antioxidant activity of the cysteine-rich metallothioneins.34 Electrospun chitosan/polyvinyl alcohol/zinc oxide nanofibrous mats have antibacterial and antioxidant properties for diabetic wound healing.35 Thus, the possible effects of the morphology of NPs on their ability to protect the skin from UV irradiation warrant study. In this work,
ZnO nanospheres, nanorods, and nanoflowers were synthesized and characterized by scanning electron microscopy. Spherical ZnO NPs were added to an FDA-approved barrier film spray, which was then used indirectly to photoprotect human fibroblast cells. Their biomolecular responses to UV light were then investigated.
2. RESULTS AND DISCUSSION The biomedical use of NPs has been of interest for the past two decades. In this work, ZnO NPs were prepared by the hydrothermal method. Figure 1 shows the prepared ZnO NPs with different morphologies. The two main parameters that were adjusted to obtain the different morphologies were the stirring rate and the pH during the reduction of the zinc ions. Figure 1a− 1802
DOI: 10.1021/acsomega.8b02321 ACS Omega 2019, 4, 1801−1809
ACS Omega
Article
c presents the pencil-like, flower-like, and spherical ZnO NPs, respectively. As shown in Figure 1a, pencil-like ZnO NPs have a mean length of ca. 100 nm and a diameter of ca. 3 μm. Figure 1b shows several hundreds of flower-like zinc oxide NPs with diameters of around 4−5 μm. Spherical zinc oxide NPs, formed with the appropriate stirring rate and pH, are shown in Figure 1c; these particles have typical diameters of
