Zhang Jing, Zhao Liyuan, Liang Along, Geng Xueyan, Hou Mengmeng, Cheng Haojie, Zhang Shouren, Yang Baocheng, Li Junbo, Chen Jian
School of Chemistry and Chemical Engineering, Henan University of Science and Technology, Luoyang, 471023, China.
Henan Key Laboratory of Nanocomposite and Applications, Institute of Nanostructured Functional Materials, Huanghe Science and Technology College, Zhengzhou, 450006, Henan, China.
J Nanobiotechnology. 2024 Dec 20;22(1):785. doi: 10.1186/s12951-024-03043-w.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease which is closely related with the overproduced reactive oxygen species (ROS), increased pro-inflammatory cytokines and disordered intestinal microbes. However, current therapeutic methods usually ignored the interrelation among the pathogenesis, and mainly focused on a single factor, inducing clinical outcomes unsatisfied. Herein, biocompatible infinite coordination polymers of drugs (Ce-SASP-RS ICPs) composed of Ce ions, FDA-approved drug sulfasalazine (SASP) and natural ingredient resistant starch (RS) were developed for synergistic treatment of IBD. The proper Ce/Ce ratio in Ce-SASP-RS ICPs can endow them with SOD-like activities, POD-like activities and •OH scavenging ability, which guarantee Ce-SASP-RS ICPs to simultaneously kill bacteria and maintain ROS balance through cascade reactions. Owing to the recovered redox balance microenvironment, SASP in Ce-SASP-RS ICPs can better play their anti-inflammatory function. Moreover, benefitting from the recovered metabolic balance of ROS and inflammatory cytokines in colon, resistant starch can also function better in modifying gut microbiota through generating short-chain fatty acids. Collectively, Ce-SASP-RS ICPs can synergistically restore intestinal metabolic microenvironment through modulating redox balance, attenuating inflammation and modifying intestinal flora. Hence, in view of the mutual influences among IBD pathogenesis, this work presents a synergistic intervention approach for effectively treating IBD.
炎症性肠病(IBD)是一种慢性胃肠道疾病,与活性氧(ROS)过度产生、促炎细胞因子增加以及肠道微生物紊乱密切相关。然而,目前的治疗方法通常忽略了发病机制之间的相互关系,主要集中在单一因素上,导致临床效果不尽人意。在此,我们开发了由铈离子、美国食品药品监督管理局(FDA)批准的药物柳氮磺胺吡啶(SASP)和天然成分抗性淀粉(RS)组成的生物相容性药物无限配位聚合物(Ce-SASP-RS ICPs),用于协同治疗IBD。Ce-SASP-RS ICPs中合适的铈/铈比例赋予它们超氧化物歧化酶(SOD)样活性、过氧化物酶(POD)样活性和羟基自由基(•OH)清除能力,这保证了Ce-SASP-RS ICPs通过级联反应同时杀灭细菌并维持ROS平衡。由于氧化还原平衡微环境的恢复,Ce-SASP-RS ICPs中的SASP能够更好地发挥其抗炎功能。此外,得益于结肠中ROS和炎性细胞因子代谢平衡的恢复,抗性淀粉还能通过产生短链脂肪酸在调节肠道微生物群方面发挥更好的作用。总的来说,Ce-SASP-RS ICPs可以通过调节氧化还原平衡、减轻炎症和调节肠道菌群来协同恢复肠道代谢微环境。因此,鉴于IBD发病机制之间的相互影响,这项工作提出了一种有效治疗IBD的协同干预方法。