Sealing the Pandora’s vase of pancreatic fistula through entrapping the digestive enzymes within a dextrorotary (D)-peptide hydrogel

Wangxiao He (), Yang Wang, Xiao Li, Yanlin Ji, Juzheng Yuan, Wenguang Yang, Siqi Yan and Jin Yan ()
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Wangxiao He: The Second Affiliated Hospital of Xi’an Jiaotong University
Yang Wang: The Second Affiliated Hospital of Xi’an Jiaotong University
Xiao Li: The Fourth Military Medical University
Yanlin Ji: The Second Affiliated Hospital of Xi’an Jiaotong University
Juzheng Yuan: The Second Affiliated Hospital of Xi’an Jiaotong University
Wenguang Yang: The First Affiliated Hospital of Xi’an Jiaotong University
Siqi Yan: The Second Affiliated Hospital of Xi’an Jiaotong University
Jin Yan: The Second Affiliated Hospital of Xi’an Jiaotong University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases.

Date: 2024
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DOI: 10.1038/s41467-024-51734-7

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