Jiang Zhengxuan, Liang Kun, Gao Xiang, Cao Fan, An Guangqi, Gui Siyu, Tang Weiwei, Du Liping, Tao Liming, Wang Xianwen
Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, Anhui, P. R. China.
The First Affiliated Hospital of Zhengzhou University, Academy of Medical Sciences of Zhengzhou University, Zhengzhou, 450052, Henan, P. R. China.
Biomater Res. 2023 Dec 12;27(1):131. doi: 10.1186/s40824-023-00451-1.
EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects.
We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation.
Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased HO release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities.
This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment.
实验性自身免疫性葡萄膜炎（EAU）是一种炎症性疾病，通常以自身炎症和自身免疫为特征，且会因活性氧（ROS）的过度产生而加重。传统的激素疗法往往有更多不良反应。迫切需要找到一种疗效更高且不良反应更少的治疗药物。
我们开发了一种铁 - 姜黄素纳米酶，其中天然抗氧化剂与铁配位形成具有优异溶解性的纳米颗粒，以发挥抗炎和清除ROS的作用来治疗EAU。通过多项实验检测纳米酶的特性。使用EAU模型大鼠检测其降低自身炎症和自身免疫的能力。使用外周血单核细胞（PBMCs）检测其抑制细胞增殖的能力。
自由基清除实验表明，纳米酶在低浓度下可降低自由基水平。体外和体内实验显示，与对照组相比，用铁 - 姜黄素纳米酶处理的组具有更低的炎症反应和ROS水平，这体现在几种关键炎症细胞因子（如干扰素 -γ、白细胞介素 -17和肿瘤坏死因子 -α）水平下调；血红素加氧酶（HO）释放减少；Th1和Th17细胞增殖受到抑制；以及眼部病理变化得到缓解。重要的是，使用普鲁士蓝染色在视网膜中检测到了铁 - 姜黄素纳米酶。此外，铁 - 姜黄素纳米酶在发挥这些生物学活性时无细胞毒性。
本研究证明了使用铁 - 姜黄素纳米酶作为纳米药物在治疗EAU中抑制炎症反应和清除ROS的可行性，表明它可能成为临床治疗中有前景的治疗剂。
