Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy

Abstract Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to...

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Main Authors: Wei Li, Chang Liu, Sichuan Wang, Naifeng Liu
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:IET Nanobiotechnology
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Online Access:https://doi.org/10.1049/nbt2.12137
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author Wei Li
Chang Liu
Sichuan Wang
Naifeng Liu
author_facet Wei Li
Chang Liu
Sichuan Wang
Naifeng Liu
author_sort Wei Li
collection DOAJ
description Abstract Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis‐specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano‐mimetic system (Ptdser‐NM‐Lipo/Fer‐1) that delivers Ferrostatin‐1 (Fer‐1) to the atherosclerotic plaque effectively, which is composed of Fer‐1‐loaded Ptdser‐modified liposomes core and neutrophils shell. Fer‐1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 μmol/ml Fer‐1 can significantly remove ROS produced by H2O2‐induced MOVAS cells and Ptdser‐NM‐Lipo/Fer‐1 revealed a 3‐fold increase in the inhibition rate of ROS than free Fer‐1 in induced‐RAW264.7, demonstrating its superior ROS‐cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM‐1, P‐selectin, E‐selectin, and chemokines released in the inflamed site, the aorta in NM‐Lipo‐treated mice displayed 1.3‐fold greater radiant efficiency than platelet membrane‐Lipo‐treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser‐NM‐Lipo/Fer‐1‐treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.
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spelling doaj-art-ff96050498be41208602a98f1cfb0d162025-02-03T06:47:18ZengWileyIET Nanobiotechnology1751-87411751-875X2023-06-0117438739510.1049/nbt2.12137Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapyWei Li0Chang Liu1Sichuan Wang2Naifeng Liu3Department of Cardiology Zhongda Hospital School of Medicine Southeast University Nanjing ChinaDepartment of Pharmaceutics State Key Laboratory of Nature Medicines China Pharmaceutical University Nanjing ChinaDepartment of Cardiology Affiliated Hospital of Yangzhou University Yangzhou University Yangzhou ChinaDepartment of Cardiology Zhongda Hospital School of Medicine Southeast University Nanjing ChinaAbstract Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis‐specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano‐mimetic system (Ptdser‐NM‐Lipo/Fer‐1) that delivers Ferrostatin‐1 (Fer‐1) to the atherosclerotic plaque effectively, which is composed of Fer‐1‐loaded Ptdser‐modified liposomes core and neutrophils shell. Fer‐1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 μmol/ml Fer‐1 can significantly remove ROS produced by H2O2‐induced MOVAS cells and Ptdser‐NM‐Lipo/Fer‐1 revealed a 3‐fold increase in the inhibition rate of ROS than free Fer‐1 in induced‐RAW264.7, demonstrating its superior ROS‐cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM‐1, P‐selectin, E‐selectin, and chemokines released in the inflamed site, the aorta in NM‐Lipo‐treated mice displayed 1.3‐fold greater radiant efficiency than platelet membrane‐Lipo‐treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser‐NM‐Lipo/Fer‐1‐treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.https://doi.org/10.1049/nbt2.12137atherosclerosisbiomimetic delivery systemdrug targetingferroptosisneutrophil
spellingShingle Wei Li
Chang Liu
Sichuan Wang
Naifeng Liu
Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
IET Nanobiotechnology
atherosclerosis
biomimetic delivery system
drug targeting
ferroptosis
neutrophil
title Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
title_full Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
title_fullStr Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
title_full_unstemmed Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
title_short Neutrophil membrane biomimetic delivery system (Ptdser‐NM‐Lipo/Fer‐1) designed for targeting atherosclerosis therapy
title_sort neutrophil membrane biomimetic delivery system ptdser nm lipo fer 1 designed for targeting atherosclerosis therapy
topic atherosclerosis
biomimetic delivery system
drug targeting
ferroptosis
neutrophil
url https://doi.org/10.1049/nbt2.12137
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AT changliu neutrophilmembranebiomimeticdeliverysystemptdsernmlipofer1designedfortargetingatherosclerosistherapy
AT sichuanwang neutrophilmembranebiomimeticdeliverysystemptdsernmlipofer1designedfortargetingatherosclerosistherapy
AT naifengliu neutrophilmembranebiomimeticdeliverysystemptdsernmlipofer1designedfortargetingatherosclerosistherapy