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

Sep 29, 2026

Severe acute pancreatitis (SAP) is a critical inflammatory disease marked by high morbidity and mortality, and existing therapies mainly provide symptomatic relief without halting inflammation at the cellular level. A macrophage membrane-coated self-assembly nanoparticle system (FePTX@CM NPs) was designed to deliver proanthocyanidin (PYD) and pentoxifylline (PTX) for targeted SAP intervention. The approach integrates particle characterization, encapsulation evaluation, and multi-method mechanistic studies to suppress macrophage PANoptosis and reduce pancreatic enzyme oversecretion, thereby alleviating inflammation progression and tissue damage in SAP models.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

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Introduction

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Journal of Advanced Research 79 (2026) 783–799 Contents lists available at ScienceDirect Journal of Advanced Research journal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare) Inﬂammation-driven biomimetic nano-polyphenol drug delivery system alleviates severe acute pancreatitis by inhibiting macrophage PANoptosis and pancreatic enzymes oversecretion Junyong Wu a,b, Hai Huang a,b, Wenjie Xu a,b, Beibei Cui c, Pengcheng Sun a,b, XinYan Hao a,b, Shihe Jiang Xuyang Hou c, Xiaoyan Qi c, Zuxing Wei c, Yimiao Cheng c, Yanwen Zheng c, Kuijie Liu c,⁎, Jun He c,⁎ a Department of Pharmacy, The Second Xiangya Hospital Central South University Changsha 410011, China b Institute of Clinical Pharmacy Central South University Changsha 410011, China c Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China c , h i g h l i g h t s • We developed a biomimetic selfassembly nanoparticle (FePTX@CM NPs) alleviate macrophage PANoptosis and enzyme oversecretion in SAP. • PYD in the NPs inhibited pancreatic enzyme release by mitochondrial ROS/Golgi stress, while PTX prevented macrophage PANoptosis by Zbp1 inhibition. • FePTX@CM NPs exhibited pancreas targeting ability due to the inﬂammation-driven macrophage membrane on its surface. g r a p h i c a l a b s t r a c t a r t i c l e i n f o Article history: Received 11 October 2024 Revised 22 March 2025 Accepted 2 April 2025 Available online 8 April 2025 Keywords: Severe acute pancreatitis PANoptosis Inﬂammation-driven Biomimetic nanoparticle Enzyme secretion a b s t r a c t 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. Abbreviations: AP, acute pancreatitis; BSA, biomacromolecules; BFA, Brefeldin A; BMDM, bone marrow-derived macrophage; CM, cell membrane; DLS, dynamic light scatter; Dex, dexamethasone; mtROS, mitochondrial reactive oxygen species; MPS, mononuclear phagocyte system; MODS, multiple organ dysfunction syndrome; NPs, nanoparticles; PYD, proanthocyanidin; PTX, pentoxifylline; SAP, severe acute pancreatitis; SIRS, systemic inﬂammatory response syndrome; TEM, transmission electron microscopy; TAC, taurocholic acid sodium. ⁎ Corresponding authors. E-mail addresses: [liukuijie@csu.edu.cn](liukuijie@csu.edu.cn) (K. Liu), [508104@csu.edu.cn](508104@csu.edu.cn) (J. He). [https://doi.org/10.1016/j.jare.2025.04.006](https://doi.org/10.1016/j.jare.2025.04.006) 2090-1232/© 2025 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). J. Wu, H. Huang, W. Xu et al. Journal of Advanced Rese

FAQs

What disease does the study focus on, and why is it challenging to treat?

The study targets severe acute pancreatitis (SAP), which has high morbidity and mortality. Treatments have largely been limited to symptom relief and have not effectively blocked inflammation progression at the cellular level.

How does the FePTX@CM nanoparticle system work in the proposed mechanism?

The nanoparticles combine proanthocyanidin (PYD) and pentoxifylline (PTX) within a macrophage membrane-coated self-assembly design. PYD inhibits pancreatic enzyme release through mitochondrial ROS/Golgi stress, while PTX prevents macrophage PANoptosis by inhibiting the Zbp1 signal pathway.

What outcomes are reported for the nanoparticle treatment in SAP models?

The system shows effective pancreas targeting, reduced systemic inflammation (including pro-inflammatory cell recruitment and activation), and minimized tissue damage in SAP mouse models, supporting its therapeutic potential for clinical SAP management.

Sep 29, 2026

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