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
,
2
,
3
;
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
2. NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan,750004,China
3. 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.
