Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles
10.1016/j.jpha.2024.01.005
- Author:
Liu DAYUE
1
;
Yang ANNING
;
Li YULIN
;
Li ZHENXIAN
;
You PEIDONG
;
Zhang HONGWEN
;
Quan SHANGKUN
;
Sun YUE
;
Zeng YALING
;
Ma SHENGCHAO
;
Xiong JIANTUAN
;
Hao YINJU
;
Li GUIZHONG
;
Liu BIN
;
Zhang HUIPING
;
Jiang YIDENG
Author Information
1. 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
- Keywords:
Homocysteine;
Atherosclerosis;
Macrophage membrane;
Prussian blue nanoparticles;
Rosuvastatin;
Gut microbes
- From:
Journal of Pharmaceutical Analysis
2024;14(9):1301-1319
- CountryChina
- Language:Chinese
-
Abstract:
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(M?m)-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.
