Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
Department of Gastroenterology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230011, China.
ACS Appl Mater Interfaces. 2024 Oct 23;16(42):56884-56901. doi: 10.1021/acsami.4c14291. Epub 2024 Oct 14.
In ulcerative colitis (UC), the formation of an inflammatory environment is due to the combined effects of excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), overproduction of proinflammatory cytokines, and disruption of immune system function. There are many kinds of traditional drugs for the clinical treatment of UC, but long-term drug use can cause toxic side effects and drug resistance and can also reduce patient compliance and other drawbacks. Hence, in light of the clinical challenges associated with UC, including the limitations of existing treatments, intense adverse reactions and the development of resistance to medications, no novel therapeutic agents that offer effective relief and maintain a high level of biosafety are urgently needed. Although many anti-inflammatory nanomedicines have been developed by researchers, the development of efficient and nontoxic nanomedicines is still a major challenge in clinical medicine. Using the natural product gallic acid and the metal compound manganese chloride, a highly effective and nontoxic multifunctional nanoenzyme was developed for the treatment of UC. Nanozymes can effectively eliminate ROS and RNS to reduce the inflammation of intestinal epithelial cells caused by oxidation, facilitate the restoration of the intestinal epithelial barrier through the upregulation of tight junction protein expression, and balance the intestinal microbiota to maintain the stability of the intestinal environment. Using a rodent model designed to mimic UC, we monitored body weight, colon length, the spleen index, and the degree of tissue damage and demonstrated that manganese gallate (MnGA) nanoparticles can reduce intestinal inflammation by clearing ROS and active nitrogen. Intestinal flora sequencing revealed that MnGA nanoparticles could regulate the intestinal flora, promote the growth of beneficial bacteria and decrease the levels of detrimental bacteria within the intestinal tract in a mouse model of UC. Thus, MnGA nanoparticles can maintain the balance of the intestinal flora. This study demonstrated that MnGA nanoparticles are excellent antioxidant and effective anti-inflammatory agents, have good biosafety, and can effectively treat UC.
在溃疡性结肠炎（UC）中，炎症环境的形成是由于活性氧（ROS）和活性氮（RNS）的过度产生、促炎细胞因子的过度产生以及免疫系统功能的破坏等综合作用所致。有许多种传统药物可用于临床治疗 UC，但长期使用药物会引起毒性副作用和耐药性，还会降低患者的依从性等缺点。因此，鉴于 UC 临床治疗中存在的诸多挑战，包括现有治疗方法的局限性、强烈的不良反应以及对药物的耐药性等，UC 迫切需要新型治疗药物，这些药物不仅需要提供有效的缓解，还需要保持较高的生物安全性。尽管研究人员已经开发出许多抗炎纳米药物，但开发高效且无毒的纳米药物仍然是临床医学中的一个主要挑战。本研究利用天然产物没食子酸和金属化合物氯化锰，开发了一种高效且无毒的多功能纳米酶，用于治疗 UC。纳米酶可以有效地清除 ROS 和 RNS，减轻氧化引起的肠道上皮细胞炎症，通过上调紧密连接蛋白表达促进肠道上皮屏障的修复，并平衡肠道微生物群，维持肠道环境的稳定性。通过建立模拟 UC 的啮齿动物模型，我们监测了体重、结肠长度、脾脏指数以及组织损伤程度，结果表明，没食子酸锰（MnGA）纳米颗粒可以通过清除 ROS 和活性氮来减轻肠道炎症。肠道菌群测序结果显示，MnGA 纳米颗粒可以调节肠道菌群，促进有益菌的生长并降低 UC 模型小鼠肠道内有害菌的水平。因此，MnGA 纳米颗粒可以维持肠道菌群的平衡。本研究表明，MnGA 纳米颗粒是一种优秀的抗氧化剂和有效的抗炎剂，具有良好的生物安全性，可有效治疗 UC。
