Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation

Autor: Yuqi Peng, Xiaofen Luo, Xinyu Wang, Enling Hu, Ruiqi Xie, Fei Lu, Weiwei Ding, Fangyin Dai, Guangqian Lan, Bitao Lu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Bioactive Materials, Vol 41, Iss , Pp 627-639 (2024)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2024.08.020
Popis: 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 Fe3+ 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.
Databáze: Directory of Open Access Journals