Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Sci Adv. 2024 Jul 26;10(30):eado7438. doi: 10.1126/sciadv.ado7438. Epub 2024 Jul 24.
Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM-mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.
设计具有胃肠道特定炎症部位靶向功能的高效口服纳米疗法，用于溃疡性结肠炎（UC）的治疗是一项具有挑战性的工作。在这里，我们专注于探索一种特定的靶向口服纳米疗法，作为“一石二鸟”，用于炎症的定向定位和氧化还原平衡的调节，从而实现 UC 治疗的“一箭双雕”效果。我们设计的纳米治疗剂 OPNs@LMWH（氧化敏感的 ε-聚赖氨酸低分子量肝素纳米粒）同时表现出特异性主动靶向作用和治疗效果。我们的结果表明，OPNs@LMWH 具有高整合素 αM 介导的免疫细胞摄取效率，并优先在炎症组织中积累。我们还通过改善氧化应激和抑制炎症相关信号通路的激活，同时增强结肠上皮的保护机制，在结肠炎小鼠的治疗实验中证实了其有效性。总之，这些发现强调了 OPNs@LMWH 的强大双重功能，使其能够有效递送到炎症部位，从而实现精确的 UC 管理。
