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

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

doi:10.1016/j.jpha.2024.01.005

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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. Targeted delivery of rosuvastatin enhances treatment of HHcy-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.005

Citation:

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. Targeted delivery of rosuvastatin enhances treatment of HHcy-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.005

Citation:

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. Targeted delivery of rosuvastatin enhances treatment of HHcy-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.005

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

doi: 10.1016/j.jpha.2024.01.005

Dayue Liu^a,b,c,
Anning Yang^a,d,e,
Yulin Li^a,b,c,
Zhenxian Li^f,
Peidong You^a,b,c,
Hongwen Zhang^a,b,c,
Shangkun Quan^a,b,c,
Yue Sun^b,d,e,
Yaling Zeng^a,b,c,
Shengchao Ma^a,b,c,
Jiantuan Xiong^b,c,
Yinju Hao^b,d,
Guizhong Li^a,b,c,
Bin Liu^{a,e,g
,
,},
Huiping Zhang^{d,e,g
,
,},
Yideng Jiang^{a,b,c
,
,}

a Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China;
b NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750004, China;
c Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, 750004, China;
d General Hospital of Ningxia Medical University, Yinchuan, 750004, China;
e College of Biology, Hunan University, Changsha, 410082, China;
f Hunan University of Chinese Medicine, First Clinical College of Traditional Chinese Medicine, Changsha, 410007, China;
g Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410000, China

Received Date: Oct. 18, 2023
Accepted Date: Jan. 11, 2024
Rev Recd Date: Jan. 06, 2024
Available Online: Jan. 15, 2024

Abstract

Abstract

Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipidlowering properties in the academic 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 longterm 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 HHcyinduced 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 ABCA1/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 biosecurity, 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 Møm-coated RVS-loaded PB NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.
- Homocysteine,
- Atherosclerosis,
- Macrophage membrane,
- Prussian blue nanoparticles,
- Rosuvastatin,
- Gut microbes

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References(51)

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