一种介孔聚多巴胺衍生的纳米药物，通过pH响应性药物释放和ROS清除来针对性和协同治疗炎症性肠病。
A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging.
发表日期：2023 Apr
作者：
Haidi Guan, Zhongwei Xu, Guangsheng Du, Qinghua Liu, Qianshan Tan, Yihui Chen, Shuaishuai Chen, Jingfeng Wu, Fengchao Wang, Jixi Zhang, Lihua Sun, Weidong Xiao
来源：
Burns & Trauma
摘要：
重复利用临床批准的药物构建新型纳米医药目前是一种非常有吸引力的治疗方法。采用刺激响应性口服纳米医药选择性富集抗炎药物和反应性氧化物清除剂(ROS)在炎症区域是治疗炎症性肠病(IBD)的有效策略。本研究报道了一种基于介孔聚多巴胺纳米颗粒(MPDA NPs)优异的药物载荷和自由基清除能力的新型纳米医药。通过在其表面启动聚丙烯酸(PAA)聚合反应，构建了一个具有pH响应性的“核-壳”结构纳米载体。然后，在碱性条件下，利用抗炎药物磺酰苯氧乙酰氨基(ＳＡＰ)和ＭＰＤＡ之间的π-π堆积和疏水作用，成功地形成了高效载药(928μg mg-1)的纳米医药(PAA@MPDA-SAP NPs)。我们的结果表明，PAA@MPDA-SAP NPs能够顺利通过上消化道，并最终积聚在发炎的结肠。通过抗炎和抗氧化的协同作用，它能够有效地减少促炎因子的表达并增强肠黏膜屏障，最终显著缓解小鼠结肠炎症状。此外，我们通过人结肠器官样物证实，PAA@MPDA-SAP NPs在炎症诱导下具有良好的生物相容性和抗炎修复能力。总之，本研究为IBD治疗纳米医药的开发提供了理论基础。 © 2023 The Authors.
Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 μ g mg-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy.© 2023 The Authors.