College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People's Republic of China.
Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang 261031, People's Republic of China.
Int J Nanomedicine. 2020 Apr 15;15:2515-2527. doi: 10.2147/IJN.S246783. eCollection 2020.
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 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy.
The β-CDs/CeO 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.
The average particle size of the blank β-CDs/CeO 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/Ce 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 HO 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 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO NPs exhibited excellent therapeutic effect.
This study may pave the way for the application of nanozyme β-CDs/CeO NPs as a powerful tool for psoriasis therapy.
活性氧（ROS）诱导的氧化应激通过引起炎症在银屑病的发病机制和进展中起关键作用。消除 ROS 的抗氧化策略可能是治疗银屑病的有效且简单的治疗选择，而具有内在抗氧化酶样活性的纳米酶尚未被探索用于银屑病治疗。本研究旨在制备β-环糊精（β-CDs）修饰的氧化铈纳米粒子（β-CDs/CeO NPs），具有载药和多模拟酶活性，用于联合治疗银屑病。
采用水热法，以未修饰的β-CDs 为保护剂合成β-CDs/CeO NPs。通过动态光散射、透射电子显微镜（TEM）、X 射线光电子能谱（XPS）和傅里叶变换红外（FTIR）光谱分析其结构、尺寸和形态。考虑到超氧化物歧化酶（SOD）和过氧化氢酶模拟活性，研究了β-CDs/CeO2 NPs 的体外抗氧化活性。负载二羟蒽醌（DIT）后，通过紫外可见分光光度计和高效液相色谱法测定载药量和释放曲线。在咪喹莫特（IMQ）诱导的小鼠模型上，基于形态评价、银屑病面积和严重程度指数（PASI）计算和炎症细胞因子表达，研究了抗银屑病疗效。
空白β-CDs/CeO NPs 的平均粒径为 60.89±0.32nm，多分散指数（PDI）为 0.12，而负载 DIT 的 NPs 的平均粒径为 79.38±1.06nm，PDI 为 0.27。TEM 结果表明，所制备的 NPs 形成了具有低分散性的均匀准球形。XPS 表明合成的 NPs 具有混合的 Ce/Ce 价态。FTIR 光谱证实 NPs 中存在β-CDs 和 DIT。在 200μg/mL 时，NPs 对超氧阴离子的抑制率可达 79.4%，在 40μg/mL 时消除 HO 的效率约为 50%，表现出优异的超氧化物歧化酶和过氧化氢酶模拟活性，从而为 ROS 介导的损伤提供了显著的抗冷冻保护。此外，表面上的β-CDs 通过主客体相互作用赋予 NPs 载药功能。DIT 的包封效率和载药量分别为 94.7%和 3.48%。体外药物释放曲线表明，DIT@β-CDs/CeO NPs 在生理条件下具有合适的 DIT 释放能力。在 IMQ 诱导的银屑病模型中，DIT@β-CDs/CeO NPs 表现出优异的治疗效果。
本研究可能为纳米酶β-CDs/CeO NPs 作为治疗银屑病的有力工具的应用铺平道路。
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