Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis
Acute pancreatitis (AP) is a highly fatal pancreatic inflammation. In recent years, synthetic nanoparticles have been extensively developed as drug carriers to address the challenges of systemic adverse reactions and lack of specificity in drug delivery. However, systemically administered nanopartic...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424004678 |
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| author | Fengyu Shi Akmal Ergashev Zhenyan Pan Hongwei Sun Lingming Kong Yuepeng Jin Tan Zhang Zhu Liu Haonan Xie Jinhui Wang Huiping Li Yi Wang Lifei Zheng Jianliang Shen Andreas Herrmann Gang Chen Hongru Kong |
| author_facet | Fengyu Shi Akmal Ergashev Zhenyan Pan Hongwei Sun Lingming Kong Yuepeng Jin Tan Zhang Zhu Liu Haonan Xie Jinhui Wang Huiping Li Yi Wang Lifei Zheng Jianliang Shen Andreas Herrmann Gang Chen Hongru Kong |
| author_sort | Fengyu Shi |
| collection | DOAJ |
| description | Acute pancreatitis (AP) is a highly fatal pancreatic inflammation. In recent years, synthetic nanoparticles have been extensively developed as drug carriers to address the challenges of systemic adverse reactions and lack of specificity in drug delivery. However, systemically administered nanoparticle therapy is rapidly cleared from circulation by the mononuclear phagocyte system (MPS), leading to suboptimal drug concentrations in inflamed tissues and suboptimal pharmacokinetics. To address this challenge, we herein demonstrate a surface masking strategy that involves coating the surface of selenylated Poria cocos polysaccharide nanoparticles with a layer of macrophage plasma membrane to circumvent MPS sequestration, thereby enhancing the therapeutic efficacy of selenylated Poria cocos polysaccharide nanoparticles. Nanoparticles encapsulated with macrophage membranes can simulate the active homing efficacy of macrophages to inflamed lesions during AP, resulting in excessive infiltration of macrophages in pancreatic inflammation sites and prolonged tissue retention time. This technique converts non-adhesive lipid nanoparticles into bioadhesive nanoparticles, increasing local tissue accumulation under inflammatory conditions, including the pancreas and vulnerable lungs. The mechanism is related to targeting pro-inflammatory macrophages. In murine models of mild and severe AP, intravenous treatment with macrophage-mimicking nanoparticles effectively reduces systemic inflammation level and diminishes the recruitment of macrophages and neutrophils. Mechanistic studies elucidate that macrophage membrane-biomimetic selenylated Poria cocos polysaccharide nanoparticles primarily mitigate pancreatic inflammation by inhibiting the AKT/mTOR pathway to reverse autophagic flux impairment. This allows us to envision that the developed biomimetic nanotherapy approach could potentially serve as a novel strategy for pancreatic drug therapy. |
| format | Article |
| id | doaj-art-296c652617bb4a129393883c80c67c8e |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-296c652617bb4a129393883c80c67c8e2025-01-17T04:52:07ZengElsevierMaterials Today Bio2590-00642025-02-0130101406Macrophage-mimicking nanotherapy for attenuation of acute pancreatitisFengyu Shi0Akmal Ergashev1Zhenyan Pan2Hongwei Sun3Lingming Kong4Yuepeng Jin5Tan Zhang6Zhu Liu7Haonan Xie8Jinhui Wang9Huiping Li10Yi Wang11Lifei Zheng12Jianliang Shen13Andreas Herrmann14Gang Chen15Hongru Kong16Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325000, ChinaWenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, ChinaNational Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, ChinaZhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, China; DWI – Leibniz-Institute for Interactive Materials, Aachen, 52056, Germany; Institute for Technical and Macromolecular Chemistry, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, 52074, Germany; Corresponding author. Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, China.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, China; Corresponding author. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China; Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, Wenzhou, Zhejiang, 325035, China; Corresponding author. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.Acute pancreatitis (AP) is a highly fatal pancreatic inflammation. In recent years, synthetic nanoparticles have been extensively developed as drug carriers to address the challenges of systemic adverse reactions and lack of specificity in drug delivery. However, systemically administered nanoparticle therapy is rapidly cleared from circulation by the mononuclear phagocyte system (MPS), leading to suboptimal drug concentrations in inflamed tissues and suboptimal pharmacokinetics. To address this challenge, we herein demonstrate a surface masking strategy that involves coating the surface of selenylated Poria cocos polysaccharide nanoparticles with a layer of macrophage plasma membrane to circumvent MPS sequestration, thereby enhancing the therapeutic efficacy of selenylated Poria cocos polysaccharide nanoparticles. Nanoparticles encapsulated with macrophage membranes can simulate the active homing efficacy of macrophages to inflamed lesions during AP, resulting in excessive infiltration of macrophages in pancreatic inflammation sites and prolonged tissue retention time. This technique converts non-adhesive lipid nanoparticles into bioadhesive nanoparticles, increasing local tissue accumulation under inflammatory conditions, including the pancreas and vulnerable lungs. The mechanism is related to targeting pro-inflammatory macrophages. In murine models of mild and severe AP, intravenous treatment with macrophage-mimicking nanoparticles effectively reduces systemic inflammation level and diminishes the recruitment of macrophages and neutrophils. Mechanistic studies elucidate that macrophage membrane-biomimetic selenylated Poria cocos polysaccharide nanoparticles primarily mitigate pancreatic inflammation by inhibiting the AKT/mTOR pathway to reverse autophagic flux impairment. This allows us to envision that the developed biomimetic nanotherapy approach could potentially serve as a novel strategy for pancreatic drug therapy.http://www.sciencedirect.com/science/article/pii/S2590006424004678Acute pancreatitisMacrophage-mimicking nanotherapySelenylated Poria cocos polysaccharide nanoparticlesAKT/mTOR pathwayAutophagy |
| spellingShingle | Fengyu Shi Akmal Ergashev Zhenyan Pan Hongwei Sun Lingming Kong Yuepeng Jin Tan Zhang Zhu Liu Haonan Xie Jinhui Wang Huiping Li Yi Wang Lifei Zheng Jianliang Shen Andreas Herrmann Gang Chen Hongru Kong Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis Materials Today Bio Acute pancreatitis Macrophage-mimicking nanotherapy Selenylated Poria cocos polysaccharide nanoparticles AKT/mTOR pathway Autophagy |
| title | Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis |
| title_full | Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis |
| title_fullStr | Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis |
| title_full_unstemmed | Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis |
| title_short | Macrophage-mimicking nanotherapy for attenuation of acute pancreatitis |
| title_sort | macrophage mimicking nanotherapy for attenuation of acute pancreatitis |
| topic | Acute pancreatitis Macrophage-mimicking nanotherapy Selenylated Poria cocos polysaccharide nanoparticles AKT/mTOR pathway Autophagy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424004678 |
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