Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticlesOA
Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles
Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(Møm)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.
Dayue Liu;Shengchao Ma;Jiantuan Xiong;Yinju Hao;Guizhong Li;Bin Liu;Huiping Zhang;Yideng Jiang;Anning Yang;Yulin Li;Zhenxian Li;Peidong You;Hongwen Zhang;Shangkun Quan;Yue Sun;Yaling Zeng
Department of Pathophysiology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,750004,China||NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan,750004,China||Ningxia Key Laboratory of Vascular Injury and Repair Research,Ningxia Medical University,Yinchuan,750004,ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan,750004,China||Ningxia Key Laboratory of Vascular Injury and Repair Research,Ningxia Medical University,Yinchuan,750004,ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan,750004,China||General Hospital of Ningxia Medical University,Yinchuan,750004,ChinaDepartment of Pathophysiology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,750004,China||College of Biology,Hunan University,Changsha,410082,China||Hunan Provincial Maternal and Child Health Care Hospital,Changsha,410000,ChinaGeneral Hospital of Ningxia Medical University,Yinchuan,750004,China||College of Biology,Hunan University,Changsha,410082,China||Hunan Provincial Maternal and Child Health Care Hospital,Changsha,410000,ChinaDepartment of Pathophysiology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,750004,China||General Hospital of Ningxia Medical University,Yinchuan,750004,China||College of Biology,Hunan University,Changsha,410082,ChinaHunan University of Chinese Medicine,First Clinical College of Traditional Chinese Medicine,Changsha,410007,ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan,750004,China||General Hospital of Ningxia Medical University,Yinchuan,750004,China||College of Biology,Hunan University,Changsha,410082,China
HomocysteineAtherosclerosisMacrophage membranePrussian blue nanoparticlesRosuvastatinGut microbes
《药物分析学报（英文）》 2024 (009)
1301-1319 / 19
This study was supported by the National Natural Science Foundation of China(Grant Nos.:U21A20343,82160088,81870225,81870332,81700404,82271626,and 82260088);the Natural Sci-ence Foundation of Ningxia Autonomous Region,China(Grant Nos.:2020AAC02021,2020AAC02038,and 2022AAC05025);the Key Research and Development Projects in Ningxia Autonomous Re-gion,China(Grant Nos.:2020BFH02003,2021BEG02033,2020BEG03008,and 2022BFH02013);the Basic Scientific Research Operating Expenses from the Public Welfare Research Institutes at the Central Level of the Chinese Academy of Medical Sciences,China(Grant No.:2019PT330002);the Ningxia Science and Tech-nology Leading Talent Project,China(Grant No.:KJT2017007);the Natural Science Foundation of Hunan Province,China(Grant No.:2022JJ40698),the School-level Special Talent Launching Project of Ningxia Medical University,China(Grant No.:XT2018015),and the Open Bidding for Selecting the Best Candidates Program of Ningxia Medical University,China(Grant No.:XJKF230106).
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