由肠道蠕动驱动的生物响应性和可转化凝聚层用于肠道出血和炎症的靶向治疗。
Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation.
作者信息
Peng Yuqi, Luo Xiaofen, Wang Xinyu, Hu Enling, Xie Ruiqi, Lu Fei, Ding Weiwei, Dai Fangyin, Lan Guangqian, Lu Bitao
机构信息
State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, 400715, China.
Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile, Chongqing, 400715, China.
出版信息
Bioact Mater. 2024 Aug 28;41:627-639. doi: 10.1016/j.bioactmat.2024.08.020. eCollection 2024 Nov.
Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time ( 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.
开发一种靶向炎症肠道以抑制出血性溃疡并减轻肠道炎症的口服原位形成水凝胶对于有效治疗溃疡性结肠炎(UC)至关重要。在此,受沙堡蠕虫粘合剂的启发,我们提出了一种与水不混溶的凝聚层(EMNs-凝胶),它在炎症部位具有从凝聚层到水凝胶的程序性转变,由富含多巴的丝素蛋白基质组成,其中嵌入了炎症响应性核壳纳米颗粒。在肠道蠕动的驱动下,EMNs-凝胶可以向前移动,并在与炎症肠道接触时立即转变为水凝胶,从而产生强大的组织粘附力,这是由于基质金属蛋白酶(MMPs)触发嵌入纳米颗粒中的铁释放以及EMNs-凝胶在炎症肠道表面的聚合物网络重排所致。广泛的体外实验和体内UC模型证实了EMNs-凝胶对炎症肠道表面的优先水凝胶化行为,实现了高效止血,并显示出延长的停留时间(48小时)。这种创新的EMNs-凝胶提供了一种非侵入性解决方案,可准确抑制UC中的严重出血并改善肠道内环境稳定状态,展现出巨大的临床应用潜力。
相似文献
ACS Appl Mater Interfaces. 2023-8-16
J Colloid Interface Sci. 2023-9-15
Adv Mater. 2019-5
引用本文的文献
本文引用的文献
Int Immunopharmacol. 2024-4-20
Appl Microbiol Biotechnol. 2023-11
Adv Healthc Mater. 2023-12
Carbohydr Polym. 2023-8-1