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. 2025 Oct;20(10):1514-1525.
doi: 10.1038/s41565-025-01979-0. Epub 2025 Aug 11.

Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages

Haizong Fang #  1 , Peidong You #  1   2 , Shengzhe Lin #  3   4 , Yuwei Wu #  1   5 , Jiajing Lin #  1 , Zelin Hou #  1 , Feihong Liang  1   4 , Changgan Chen  1 , Zhiyuan Wang  1 , Linlin Chen  6 , Shihan Zhang  6 , Xiaolan Chen  7 , Kui Zhao  8 , Fengchun Lu  1 , Minggui Pan  9 , Yundong Zhou  10 , Chengliang Yin  11 , João Conde  12 , Heguang Huang  13 , Yu Pan  14   15
Affiliations

Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages

Haizong Fang et al. Nat Nanotechnol. 2025 Oct.

Abstract

Acute pancreatitis (AP) is associated with high mortality rates and is characterized by increased cell death of acinar cells, with the premature release and activation of digestive enzymes. In its acute phase, AP is accompanied by increased efferocytosis, to clear phagocytic apoptotic cells; annexin A1 (Anxa1) is key to efferocytosis, but its role in AP is still unknown. Here we show that Anxa1 deficiency abrogates the efferocytosis of pancreatic macrophages, resulting in the accumulation of apoptotic acinar cells and necrosis. Moreover, we showed that nano-liposomes loaded with Anxa1 mRNA alleviate AP pathology by suppressing the cGAMP-cGAS-STING pathway and restoring efferocytosis in macrophages. Our results reveal the crucial function of Anxa1 in the efferocytosis of macrophages during AP and illustrate a novel nanotechnology treatment approach for AP that may be of potential therapeutic value in humans.

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Conflict of interest statement

Competing interests: J.C. is a co-founder and shareholder of TargTex S.A. Targeted therapeutics for Glioblastoma Multiforme. J.C. is also a member of the Global Burden Disease (GBD) consortium from Institute for Health Metrics and Evaluation (IHME), University of Washington. Y.P., F. Liang and P.Y. are authors of a provisional patent (202411349874.8, China) based on this paper. The other authors declare no competing interests.

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