Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery

Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial...

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Main Authors: Kaichao Hu, Junrui Ye, Pinglong Fan, Ruifang Zheng, Shasha Wang, Ye Peng, Yuan Ruan, Xu Yan, Zhao Zhang, Shifeng Chu, Naihong Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-05-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25000179
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author Kaichao Hu
Junrui Ye
Pinglong Fan
Ruifang Zheng
Shasha Wang
Ye Peng
Yuan Ruan
Xu Yan
Zhao Zhang
Shifeng Chu
Naihong Chen
author_facet Kaichao Hu
Junrui Ye
Pinglong Fan
Ruifang Zheng
Shasha Wang
Ye Peng
Yuan Ruan
Xu Yan
Zhao Zhang
Shifeng Chu
Naihong Chen
author_sort Kaichao Hu
collection DOAJ
description Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.
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publisher KeAi Communications Co., Ltd.
record_format Article
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spelling doaj-art-dc44cf40aa7c4673be432c3382218c4d2025-01-24T04:45:32ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-0147181197Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recoveryKaichao Hu0Junrui Ye1Pinglong Fan2Ruifang Zheng3Shasha Wang4Ye Peng5Yuan Ruan6Xu Yan7Zhao Zhang8Shifeng Chu9Naihong Chen10State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; College of Pharmacy, Changchun University of Chinese Medicine, China, Changchun, 130117, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, ChinaXinjiang Institute of Materia Medica, Urumqi, 830004, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Corresponding author. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Road, Beijing, 100050, China.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Corresponding author. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Road, Beijing, 100050, China.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; College of Pharmacy, Changchun University of Chinese Medicine, China, Changchun, 130117, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Xinjiang Institute of Materia Medica, Urumqi, 830004, China; Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China; Corresponding author. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Road, Beijing, 100050, China.Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.http://www.sciencedirect.com/science/article/pii/S2452199X25000179Stroke recoveryNanovesiclesRg1NeutrophilMicrogliaNeovascularization
spellingShingle Kaichao Hu
Junrui Ye
Pinglong Fan
Ruifang Zheng
Shasha Wang
Ye Peng
Yuan Ruan
Xu Yan
Zhao Zhang
Shifeng Chu
Naihong Chen
Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
Bioactive Materials
Stroke recovery
Nanovesicles
Rg1
Neutrophil
Microglia
Neovascularization
title Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
title_full Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
title_fullStr Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
title_full_unstemmed Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
title_short Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery
title_sort targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside rg1 nanovesicles promotes stroke recovery
topic Stroke recovery
Nanovesicles
Rg1
Neutrophil
Microglia
Neovascularization
url http://www.sciencedirect.com/science/article/pii/S2452199X25000179
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