Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis

Lingyun Wu,1,2,* Guoyan Liu,2,* Wenyu Wang,1 Ruobing Liu,1 Lingyan Liao,1 Ni Cheng,1 Wentong Li,3 Weifen Zhang,1 Dejun Ding1 1College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Weifang Me...

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Autores principales:	Wu L, Liu G, Wang W, Liu R, Liao L, Cheng N, Li W, Zhang W, Ding D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	ceria nanoparticles reactive oxygen species mimic-enzyme dithranol anti-psoriatic drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f6759c7b67e74ee589a386e275717911
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id	oai:doaj.org-article:f6759c7b67e74ee589a386e275717911
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	ceria nanoparticles reactive oxygen species mimic-enzyme dithranol anti-psoriatic drug delivery Medicine (General) R5-920
spellingShingle	ceria nanoparticles reactive oxygen species mimic-enzyme dithranol anti-psoriatic drug delivery Medicine (General) R5-920 Wu L Liu G Wang W Liu R Liao L Cheng N Li W Zhang W Ding D Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
description	Lingyun Wu,1,2,* Guoyan Liu,2,* Wenyu Wang,1 Ruobing Liu,1 Lingyan Liao,1 Ni Cheng,1 Wentong Li,3 Weifen Zhang,1 Dejun Ding1 1College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang 261031, People’s Republic of China; 3Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weifen Zhang; Dejun DingCollege of Pharmacy, Weifang Medical University, 7166# Baotong West Street, Weifang, Shandong 261053, People’s Republic of ChinaTel/Fax +(86)-0536-8462051Email zhangwf@wfmc.edu.cn; dejunding@wfmc.edu.cnPurpose: 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/CeO2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.Methods: The β-CDs/CeO2 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/CeO2 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 Ce3+/Ce4+ 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 H2O2 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/CeO2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO2 NPs exhibited excellent therapeutic effect.Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO2 NPs as a powerful tool for psoriasis therapy.Keywords: ceria nanoparticles, reactive oxygen species, mimic-enzyme, dithranol, anti-psoriatic, drug delivery
format	article
author	Wu L Liu G Wang W Liu R Liao L Cheng N Li W Zhang W Ding D
author_facet	Wu L Liu G Wang W Liu R Liao L Cheng N Li W Zhang W Ding D
author_sort	Wu L
title	Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
title_short	Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
title_full	Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
title_fullStr	Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
title_full_unstemmed	Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis
title_sort	cyclodextrin-modified ceo2 nanoparticles as a multifunctional nanozyme for combinational therapy of psoriasis
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/f6759c7b67e74ee589a386e275717911
work_keys_str_mv	AT wul cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT liug cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT wangw cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT liur cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT liaol cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT chengn cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT liw cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT zhangw cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis AT dingd cyclodextrinmodifiedceo2nanoparticlesasamultifunctionalnanozymeforcombinationaltherapyofpsoriasis
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spelling	oai:doaj.org-article:f6759c7b67e74ee589a386e2757179112021-12-02T09:56:14ZCyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis1178-2013https://doaj.org/article/f6759c7b67e74ee589a386e2757179112020-04-01T00:00:00Zhttps://www.dovepress.com/cyclodextrin-modified-ceo2-nanoparticles-as-a-multifunctional-nanozyme-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lingyun Wu,1,2,* Guoyan Liu,2,* Wenyu Wang,1 Ruobing Liu,1 Lingyan Liao,1 Ni Cheng,1 Wentong Li,3 Weifen Zhang,1 Dejun Ding1 1College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang 261031, People’s Republic of China; 3Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weifen Zhang; Dejun DingCollege of Pharmacy, Weifang Medical University, 7166# Baotong West Street, Weifang, Shandong 261053, People’s Republic of ChinaTel/Fax +(86)-0536-8462051Email zhangwf@wfmc.edu.cn; dejunding@wfmc.edu.cnPurpose: 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/CeO2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.Methods: The β-CDs/CeO2 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/CeO2 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 Ce3+/Ce4+ 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 H2O2 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/CeO2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO2 NPs exhibited excellent therapeutic effect.Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO2 NPs as a powerful tool for psoriasis therapy.Keywords: ceria nanoparticles, reactive oxygen species, mimic-enzyme, dithranol, anti-psoriatic, drug deliveryWu LLiu GWang WLiu RLiao LCheng NLi WZhang WDing DDove Medical Pressarticleceria nanoparticlesreactive oxygen speciesmimic-enzymedithranolanti-psoriaticdrug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2515-2527 (2020)

Cyclodextrin-Modified CeO2 Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis

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