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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      Cyclodextrin-Modified CeO 2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis

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          Abstract

          Purpose

          Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO 2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.

          Methods

          The β-CDs/CeO 2 NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression.

          Results

          The average particle size of the blank β-CDs/CeO 2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce 3+/Ce 4+ valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H 2O 2 efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host–guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@β-CDs/CeO 2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO 2 NPs exhibited excellent therapeutic effect.

          Conclusion

          This study may pave the way for the application of nanozyme β-CDs/CeO 2 NPs as a powerful tool for psoriasis therapy.

          Most cited references43

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          Pathogenesis and clinical features of psoriasis.

          Christopher EM Griffiths, Jonathan Barker (2007)
          Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.
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            Fundamentals and Catalytic Applications of CeO2-Based Materials.

            Tiziano Montini, Michele Melchionna, Matteo Monai … (2016)
            Cerium dioxide (CeO2, ceria) is becoming an ubiquitous constituent in catalytic systems for a variety of applications. 2016 sees the 40(th) anniversary since ceria was first employed by Ford Motor Company as an oxygen storage component in car converters, to become in the years since its inception an irreplaceable component in three-way catalysts (TWCs). Apart from this well-established use, ceria is looming as a catalyst component for a wide range of catalytic applications. For some of these, such as fuel cells, CeO2-based materials have almost reached the market stage, while for some other catalytic reactions, such as reforming processes, photocatalysis, water-gas shift reaction, thermochemical water splitting, and organic reactions, ceria is emerging as a unique material, holding great promise for future market breakthroughs. While much knowledge about the fundamental characteristics of CeO2-based materials has already been acquired, new characterization techniques and powerful theoretical methods are deepening our understanding of these materials, helping us to predict their behavior and application potential. This review has a wide view on all those aspects related to ceria which promise to produce an important impact on our life, encompassing fundamental knowledge of CeO2 and its properties, characterization toolbox, emerging features, theoretical studies, and all the catalytic applications, organized by their degree of establishment on the market.
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              Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease.

              Hyek Kwon, Moon-Yong Cha, Dokyoon Kim … (2016)
              Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer's disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer's disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer's disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (iso-abbrev): Int J Nanomedicine
                Journal ID (publisher-id): IJN
                Journal ID (pmc): intjnano
                Title: International Journal of Nanomedicine
                Publisher: Dove
                ISSN (Print): 1176-9114
                ISSN (Electronic): 1178-2013
                Publication date (Electronic): 15 April 2020
                Publication date Collection: 2020
                Volume: 15
                Pages: 2515-2527
                Affiliations
                [1 ]College of Pharmacy, Weifang Medical University , Weifang, Shandong 261053, People’s Republic of China
                [2 ]Department of Dermatology, Affiliated Hospital of Weifang Medical University , Weifang 261031, People’s Republic of China
                [3 ]Department of Pathology, Weifang Medical University , Weifang, Shandong 261053, People’s Republic of China
                Author notes
                Correspondence: Weifen Zhang; Dejun Ding College of Pharmacy, Weifang Medical University , 7166# Baotong West Street, Weifang, Shandong261053, People’s Republic of China Tel/Fax +(86)-0536-8462051 Email zhangwf@wfmc.edu.cn; dejunding@wfmc.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-4073-0548
                http://orcid.org/0000-0003-4736-2474
                http://orcid.org/0000-0001-7809-7963
                Article
                Publisher ID: 246783
                DOI: 10.2147/IJN.S246783
                PMC ID: 7170634
                SO-VID: 5d6671a4-3632-4cdb-86d5-bc4142de93c2
                Copyright © © 2020 Wu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 21 January 2020
                Date accepted : 24 March 2020
                Page count
                Figures: 6, References: 54, Pages: 13
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: ceria nanoparticles,reactive oxygen species,mimic-enzyme,dithranol,anti-psoriatic,drug delivery
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: ceria nanoparticles, reactive oxygen species, mimic-enzyme, dithranol, anti-psoriatic, drug delivery

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