2. Academic Validation
  3. Targeted inhibition of M2 macrophages polarization via a PDC attenuates chronic pancreatitis through the PPARα pathway

Targeted inhibition of M2 macrophages polarization via a PDC attenuates chronic pancreatitis through the PPARα pathway

  • iScience. 2026 Jan 29;29(2):114839. doi: 10.1016/j.isci.2026.114839.
Xin Kong 1 2,  Xufeng Tao 1,  Hong Xiang 3,  Fangyue Guo 3,  Yu Wu 3 4,  Jing Lv 1 2,  Xinya Zhao 1 2,  Xiaonan Zhang 3 4,  Zhiwen Zhai 5,  Deshi Dong 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
  • 2 College of Pharmacy, Dalian Medical University, Dalian 116044, China.
  • 3 Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
  • 4 Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116011, China.
  • 5 Centre for Animal Experiment, Wuhan University, Wuhan 430072, China.
PMID: 41716994 DOI: 10.1016/j.isci.2026.114839
Abstract

This study examines the pivotal role of M2-type macrophages in chronic pancreatitis (CP) and the existing challenges in targeted intervention. A peptide-drug conjugate (PDC) was developed for this investigation by linking the S100A9 inhibitor Tasquinimod to a peptide that selectively targets M2 macrophages. In experimental models, this conjugate demonstrated a marked capacity to alleviate pancreatic injury, inflammation, and fibrotic progression. Compared to the free drug, it showed enhanced targeting, greater efficacy, and a reduced toxicity profile without causing significant damage to vital organs. Mechanistic analysis indicated that its effects are mediated through the activation of the Peroxisome Proliferator-activated Receptor α (PPARα) signaling pathway, leading to suppressed phosphorylation of the NF-κB p65 subunit and c-Jun, which in turn inhibits M2 macrophage polarization. These results uncover a functional mechanism and provide a foundation for developing targeted immunomodulatory therapies against CP.

Keywords

Biotechnology; Cell biology; Microenvironment.

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