2. Academic Validation
  3. Inflammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion

Inflammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion

  • J Adv Res. 2025 Apr 8:S2090-1232(25)00225-5. doi: 10.1016/j.jare.2025.04.006.
Junyong Wu 1,  Hai Huang 1,  Wenjie Xu 1,  Beibei Cui 2,  Pengcheng Sun 1,  XinYan Hao 1,  Shihe Jiang 2,  Xuyang Hou 2,  Xiaoyan Qi 2,  Zuxing Wei 2,  Yimiao Cheng 2,  Yanwen Zheng 2,  Kuijie Liu 3,  Jun He 4
Affiliations

Affiliations

  • 1 Department of Pharmacy, The Second Xiangya Hospital Central South University Changsha 410011, China; Institute of Clinical Pharmacy Central South University Changsha 410011, China.
  • 2 Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
  • 3 Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: liukuijie@csu.edu.cn.
  • 4 Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: 508104@csu.edu.cn.
PMID: 40210149 DOI: 10.1016/j.jare.2025.04.006
Abstract

Introduction: Severe acute pancreatitis (SAP) is a critical inflammatory disease with high morbidity and mortality. Current treatments focused on symptomatic relief but failed to prevent inflammation progression in cellular level.

Objectives: In order to develop an SAP-targeting drug delivery system to alleviate SAP in cellular level and illustrate its mechanism, we explored the use of proanthocyanidin (PYD) and pentoxifylline (PTX) loaded into macrophage membrane-coated self-assembly nanoparticles (FePTX@CM NPs) for targeted SAP treatment. The combination application of these two drugs was innovative in SAP aid.

Methods: We developed the NPs by self-assembly strategy and cell membrane coating. Its particle size and zeta potential were measured by dynamic light scatter (DLS). The morphology of the NPs was observed by transmission electron microscopy (TEM). And the encapsulation efficiency was evaluated by nano-flow cytometry. The total protein profile was determined via Coomassie brilliant blue. We explore the mechanism of our NPs against SAP in cellular and animal levels. Bioinformatics approaches, TEM, immunofluorescent assay and co-immunoprecipitation were performed to comprehensively explain the specific anti-SAP mechanism of FePTX@CM NPs.

Results: After inflammation-driven targeting, PYD in the NPs inhibited pancreatic amylase and Lipase release by suppressing mitochondrial Reactive Oxygen Species (mtROS)/Golgi stress, while PTX prevented SAP-associated macrophage PANoptosis by inhibiting Zbp1 signal pathway. The protection effect of these biomimetic NPs worked from different aspects to alleviate SAP symptoms and inflammation progression in relative cells.

Conclusion: The FePTX@CM NPs demonstrated effective pancreas targeting, reduced systemic inflammation especially pro-inflammatory cell recruitment and activation, and minimized tissue damage in SAP mouse models, offering a promising therapeutic strategy for clinical SAP management.

Keywords

Biomimetic nanoparticle; Enzyme secretion; Inflammation-driven; PANoptosis; Severe acute pancreatitis.

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