Gao Yanyao, Zou Jing, Chen Bo, Cao Yuhao, Hu Datao, Zhang Yuchen, Zhao Xinxin, Wen Jinpeng, Liu Kailai, Wang Ke
Department of Urology, Tangdu Hospital, Air Force Medical University, Xi'an 710038.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
Biomater Sci. 2023 Jan 17;11(2):618-629. doi: 10.1039/d2bm01256a.
Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease often characterized by rapid progression and frequent comorbidities that make its treatment challenging. In colonic ulcers of UC patients, myeloperoxidase (MPO) is highly expressed, which results in an abundance of macrophages and reactive oxygen species. This study developed an active MPO-targeting hyaluronic acid/serotonin ceria nanoenzyme (HA-5-HT@CeO) using the electrostatic interaction between CeO nanoparticles, 5-hydroxyserotonin-cerium oxide and hyaluronic acid. Based on the dual targeting effects of MPO and the macrophage CD44+ receptor in locating the inflammatory site in conjunction with the inflammatory area of the colon through electrostatic action, CeO nanoparticles along with multiple similar enzymes were used to eliminate O, HO and ˙OH and other reactive oxygen species, achieving targeted repair of the intestinal epithelial barrier through the elimination of inflammatory factors. In studies involving pharmacodynamics and DSS-induced animal models of acute colitis , HA-5-HT@CeO has been shown to reduce inflammation further and treat ulcerative colitis compared to traditional drugs. Additionally, active targeting of MPO inflammation can lead to accurate drug delivery to the site and can minimize the side effects associated with the drug. HA-5-HT@CeO is a promising novel drug for the treatment of ulcerative colitis. In addition to illustrating the benefits of this novel nanodrug delivery in treating ulcerative colitis compared to traditional medications, this study provides theoretical and experimental support for its application to any targeted therapy for ulcerative colitis.
溃疡性结肠炎（UC）是一种慢性非特异性炎症性肠病，其特点通常是进展迅速且合并症频繁，这使得其治疗具有挑战性。在UC患者的结肠溃疡中，髓过氧化物酶（MPO）高度表达，这导致大量巨噬细胞和活性氧的产生。本研究利用CeO纳米颗粒、5-羟色胺-氧化铈与透明质酸之间的静电相互作用，开发了一种主动靶向MPO的透明质酸/血清素二氧化铈纳米酶（HA-5-HT@CeO）。基于MPO和巨噬细胞CD44+受体在通过静电作用定位炎症部位并结合结肠炎症区域的双重靶向作用，CeO纳米颗粒与多种类似酶一起用于消除O₂、H₂O₂和˙OH等活性氧，通过消除炎症因子实现肠道上皮屏障的靶向修复。在涉及药效学和DSS诱导的急性结肠炎动物模型的研究中，与传统药物相比，HA-5-HT@CeO已被证明能进一步减轻炎症并治疗溃疡性结肠炎。此外，对MPO炎症的主动靶向可导致药物准确递送至该部位，并可将与药物相关的副作用降至最低。HA-5-HT@CeO是一种有前景的治疗溃疡性结肠炎的新型药物。除了说明这种新型纳米药物递送在治疗溃疡性结肠炎方面与传统药物相比的优势外，本研究还为其应用于溃疡性结肠炎的任何靶向治疗提供了理论和实验支持。
