首页|Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles

Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles

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  • 国家科技期刊平台
  • NETL
  • NSTL
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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.

HomocysteineAtherosclerosisMacrophage membranePrussian blue nanoparticlesRosuvastatinGut microbes

Dayue Liu、Anning Yang、Yulin Li、Zhenxian Li、Peidong You、Hongwen Zhang、Shangkun Quan、Yue Sun、Yaling Zeng、Shengchao Ma、Jiantuan Xiong、Yinju Hao、Guizhong Li、Bin Liu、Huiping Zhang、Yideng Jiang

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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,China

General Hospital of Ningxia Medical University,Yinchuan,750004,China

College of Biology,Hunan University,Changsha,410082,China

Hunan University of Chinese Medicine,First Clinical College of Traditional Chinese Medicine,Changsha,410007,China

Hunan Provincial Maternal and Child Health Care Hospital,Changsha,410000,China

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2024

10.1016/j.jpha.2024.01.005

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(9)