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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1442876

PepT1-targeted Nanodrug Based on Co-Assembly of Antiinflammatory Peptide and Immunosuppressant for Combined Treatment of Acute and Chronic DSS-induced ColitiS

Provisionally accepted
Daifang Zhang Daifang Zhang *longqi Jiang longqi Jiang Fengxu Yu Fengxu Yu Pijun Yan Pijun Yan Yong Liu Yong Liu *Ya Wu Ya Wu *Xi Yang Xi Yang *
  • The Affiliated Hospital of Southwest Medical University, Luzhou, China

The final, formatted version of the article will be published soon.

    Colitis, as a chronic and recurrent inflammatory bowel diseases with limited therapeutic outcomes, is characterized by immune disorders and intestinal barrier dysfunction. Herein, we aim to develop KPV-FK506 nanoparticles (NPs) based on the co-assembly of an anti-inflammatory peptide (Lysine-pro-valine, KPV) and an immunosuppressant (FK506) for the combined treatment of colitis by regulating immune and intestinal barrier disorders. Notably, KPV can possess targeting ability for oligopeptide transporter 1 (PepT1) overexpressed in colonic epithelial and macrophages during colitis. In our study, we found NPs could be efficiently internalized by Caco-2 and RAW264.7 cells as well, localized to the inflamed colon preferentially. After administering with NPs, mice with DSS-induced acute or chronic colitis exhibited significant improvement in body weight, colon length, and disease activity index, which exposed that NPs could ameliorate murine colitis effectively. Moreover, treatment with NPs decreased levels of MPO, NO, ROS, and suppressed the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), which performed similarly to the healthy group. Furthermore, the treatment led to a notable reduction of the expressions of CD68 and CD3, which represented reduced infiltration of macrophages and T-lymphocytes. Additionally, the expression levels of tight junction proteins Claudin-5, Occludin-1, and ZO-1 were significantly diminished in the DSS group but were substantially restored in the NPs group, surpassing those observed in the KPV and FK506 groups. Our findings indicated that NPs can reduce inflammation and enhance epithelial barrier integrity by decreasing the infiltration of macrophages and T-lymphocytes. Collectively, those results demonstrated the effectively therapeutic outcome after using NPs in both acute and chronic colitis, suggesting that NPs can be as a potential therapeutic candidate for colitis.

    Keywords: Colitis, PepT1-tageting, combined treatment, KPV, FK506

    Received: 03 Jun 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Zhang, Jiang, Yu, Yan, Liu, Wu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Daifang Zhang, The Affiliated Hospital of Southwest Medical University, Luzhou, China
    Yong Liu, The Affiliated Hospital of Southwest Medical University, Luzhou, China
    Ya Wu, The Affiliated Hospital of Southwest Medical University, Luzhou, China
    Xi Yang, The Affiliated Hospital of Southwest Medical University, Luzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.