Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-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

Volume 14 Issue 9

Sep. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(9): 100937

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 hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis, 2024, 14(9): 100937. 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 hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis, 2024, 14(9): 100937. 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 hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles[J]. Journal of Pharmaceutical Analysis, 2024, 14(9): 100937. doi: 10.1016/j.jpha.2024.01.005

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Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-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

Funds:

This study was supported by the National Natural Science Foundation of China (Grant Nos.: U21A20343, 82160088, 81870225, 81870332, 81700404, 82271626, and 82260088)

the Natural Science Foundation of Ningxia Autonomous Region, China (Grant Nos.: 2020AAC02021, 2020AAC02038, and 2022AAC05025)

the Key Research and Development Projects in Ningxia Autonomous Region, 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 Technology 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).

Received Date: Oct. 18, 2023
Accepted Date: Jan. 11, 2024
Rev Recd Date: Jan. 06, 2024
Publish Date: Jan. 13, 2024

Abstract

Abstract

Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering 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 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 biosecurity, 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.
- Homocysteine,
- Atherosclerosis,
- Macrophage membrane,
- Prussian blue nanoparticles,
- Rosuvastatin,
- Gut microbes

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References(51)

References

[1]	N. Zhang, L. Zhu, X. Wu, et al., The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis, Atherosclerosis 334 (2021) 39-47.
[2]	X. Lu, Impact of macrophages in atherosclerosis, Curr. Med. Chem. 23 (2016) 1926-1937.
[3]	J. Shah, V. Lingiah, N. Pyrsopoulos, et al., Acute liver injury in a patient treated with rosuvastatin: A rare adverse effect, Gastroenterology Res. 12 (2019) 263-266.
[4]	M. Cheraghi, B. Negahdari, H. Daraee, et al., Heart targeted nanoliposomal/nanoparticles drug delivery: An updated review, Biomed. Pharmacother. 86 (2017) 316-323.
[5]	Z. Qin, Y. Li, N. Gu, Progress in applications of Prussian blue nanoparticles in biomedicine, Adv. Healthc. Mater. 7 (2018), e1800347.
[6]	Y. Zhang, Y. Yin, W. Zhang, et al., Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic Prussian blue analogues boycott atherosclerosis, J. Nanobiotechnology 19 (2021), 161.
[7]	J. Lopes, D. Lopes, M. Pereira-Silva, et al., Macrophage cell membrane-cloaked nanoplatforms for biomedical applications, Small Methods 6 (2022), e2200289.
[8]	R. Wang, Y. Wang, N. Mu, et al., Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in ApoE-deficient mice, Lab Invest. 97 (2017) 922-934.
[9]	J. Shi, Y. Zhao, K. Wang, et al., Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death, Nature 526 (2015) 660-665.
[10]	P. Yu, X. Zhang, N. Liu, et al., Pyroptosis: mechanisms and diseases, Signal Transduct. Target. Ther. 6 (2021), 128.
[11]	S. Ma, Y. Hao, Y. Jiao, et al., Homocysteine-induced oxidative stress through TLR4/NF-κB/DNMT1-mediated LOX-1 DNA methylation in endothelial cells, Mol. Med. Rep. 16 (2017) 9181-9188.
[12]	M. Xu, Z. Ye, X. Zhao, et al., Deficiency of tenascin-C attenuated cardiac injury by inactivating TLR4/NLRP3/caspase-1 pathway after myocardial infarction, Cell. Signal. 86 (2021), 110084.
[13]	Z. Hong, X. Zhang, T. Zhang, et al., The ROS/GRK2/HIF-1α/NLRP3 pathway mediates pyroptosis of fibroblast-like synoviocytes and the regulation of monomer derivatives of paeoniflorin, Oxid. Med. Cell. Longev. 2022 (2022), 4566851.
[14]	R. Chen, T. Chen, Z. Zhou, et al., Integrated pyroptosis measurement and metabolomics to elucidate the effect and mechanism of tangzhiqing on atherosclerosis, Front. Physiol. 13 (2022), 937737.
[15]	Y. Yang, Y. Zhang, Y. Xu, et al., Dietary methionine restriction improves the gut microbiota and reduces intestinal permeability and inflammation in high-fat-fed mice, Food Funct. 10 (2019) 5952-5968.
[16]	Q. Chen, C. Wang, F. Zhao, et al., Effects of methionine partially replaced by methionyl-methionine dipeptide on intestinal function in methionine-deficient pregnant mice, J. Anim. Physiol. Anim. Nutr. 103 (2019) 1610-1618.
[17]	M. Witkowski, T.L. Weeks, S.L. Hazen, Gut microbiota and cardiovascular disease, Circ. Res. 127 (2020) 553-570.
[18]	X. Liang,H. Li,X. Li, et al., Highly sensitive H₂O₂-scavenging nano-bionic system for precise treatment of atherosclerosis, Acta Pharm. Sin. B 13 (2023) 372-389.
[19]	X. Zhang, Y. Qin, X. Wan, et al., Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities, J. Transl. Med. 19 (2021), 62.
[20]	J.D. Nickels, K.S. Bonifer, R.R. Tindall, et al., Improved chemical and isotopic labeling of biomembranes in Bacillus subtilis by leveraging CRISPRi inhibition of beta-ketoacyl-ACP synthase (fabF), Front. Mol. Biosci. 9 (2022), 1011981.
[21]	X. Hou, H. Zeng, X. Chi, et al., Pathogen receptor membrane-coating facet structures boost nanomaterial immune escape and antibacterial performance, Nano Lett. 21 (2021) 9966-9975.
[22]	J.W. Calderwood, J.M. Williams, M.D. Morgan, et al., ANCA induces beta2 integrin and CXC chemokine-dependent neutrophil-endothelial cell interactions that mimic those of highly cytokine-activated endothelium, J Leukoc. Biol. 77 (2005) 33-43.
[23]	X. Chen, Q. Wang, L. Liu, et al., Double-sided effect of tumor microenvironment on platelets targeting nanoparticles, Biomaterials 183 (2018) 258-267.
[24]	N. Khatoon, Z. Zhang, C. Zhou, et al., Macrophage membrane coated nanoparticles: A biomimetic approach for enhanced and targeted delivery, Biomater. Sci. 10 (2022) 1193-1208.
[25]	M.F. Linton, V.R. Babaev, J. Huang, et al., Macrophage apoptosis and efferocytosis in the pathogenesis of atherosclerosis, Circ. J. 80 (2016) 2259-2268.
[26]	M. Lombardi, M.E. Mantione, D. Baccellieri, et al., P2X7 receptor antagonism modulates IL-1β and MMP9 in human atherosclerotic vessels, Sci. Rep. 7 (2017), 4872.
[27]	J. Geng, H. Xu, W. Fu, et al., Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE^-/- mice by suppressing endoplasmic reticulum stress, Exp. Ther. Med. 20 (2020) 550-560.
[28]	S. Liu, J. Tao, F. Duan, et al., HHcy induces pyroptosis and atherosclerosis via the lipid raft-mediated NOX-ROS-NLRP3 inflammasome pathway in ApoE^-/- mice, Cells 11 (2022), 2438.
[29]	J. Yang, L. Wise, K.I. Fukuchi, TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer's disease, Front. Immunol. 11 (2020), 724.
[30]	A. Ajoolabady, Y. Bi, D.J. McClements, et al., Melatonin-based therapeutics for atherosclerotic lesions and beyond: Focusing on macrophage mitophagy, Pharmacol. Res. 176 (2022), 106072.
[31]	Y.-W. Wang, H.-Z. Dong, Y.-X. Tan, et al., HIF-1α-regulated lncRNA-TUG1 promotes mitochondrial dysfunction and pyroptosis by directly binding to FUS in myocardial infarction, Cell Death Discov. 8 (2022), 178.
[32]	X. Ma, J. Hao, J. Wu, et al., Prussian blue nanozyme as a pyroptosis inhibitor alleviates neurodegeneration, Adv. Mater. 34 (2022), e2106723.
[33]	C. Xiao, C. Tong, J. Fan, et al., Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation, J. Control. Release 339 (2021) 259-273.
[34]	A. Chen, Z. Chen, Y. Zhou, et al., Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation, Cell Death Dis. 12 (2021), 78.
[35]	C. Thomas, D. Leleu, D. Masson, Cholesterol and HIF-1α: Dangerous liaisons in atherosclerosis, Front. Immunol. 13 (2022), 868958.
[36]	I. Hussain, S. Waheed, K.A. Ahmad, et al., Scutellaria baicalensis targets the hypoxia-inducible factor-1α and enhances cisplatin efficacy in ovarian cancer, J. Cell. Biochem. 119 (2018) 7515-7524.
[37]	L. Shen, H. Li, W. Chen, et al., Integrated application of transcriptome and metabolomics reveals potential therapeutic targets for the polarization of atherosclerotic macrophages, Biochim. Biophys. Acta Mol. Basis Dis. 1868 (2022), 166550.
[38]	L. Anto, C.N. Blesso, Interplay between diet, the gut microbiome, and atherosclerosis: Role of dysbiosis and microbial metabolites on inflammation and disordered lipid metabolism, J. Nutr. Biochem. 105 (2022), 108991.
[39]	H. Jian, Q. Xu, X. Wang, et al., Amino acid and fatty acid metabolism disorders trigger oxidative stress and inflammatory response in excessive dietary valine-induced NAFLD of laying hens, Front. Nutr. 9 (2022), 849767.
[40]	R. Cazzola, M. Rondanelli, N-oleoyl-phosphatidyl-ethanolamine and epigallo catechin-3-gallate mitigate oxidative stress in overweight and class I obese people on a low-calorie diet, J. Med. Food 23 (2020) 319-325.
[41]	H.S. Lee, S.J. Yun, J.M. Ha, et al., Prostaglandin D₂ stimulates phenotypic changes in vascular smooth muscle cells, Exp. Mol. Med. 51 (2019) 1-10.
[42]	H. Wu, M. Zhang, W. Li, et al., Stachydrine attenuates IL-1β-induced inflammatory response in osteoarthritis chondrocytes through the NF-κB signaling pathway, Chem. Biol. Interact. 326 (2020), 109136.
[43]	Y. Du, X. Gu, H. Meng, et al., Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-κB and NLRP3 inflammasome, Am. J. Transl. Res. 10 (2018) 4235-4246.
[44]	X. Gao, Y. Ruan, X. Zhu, et al., Deoxycholic acid promotes pyroptosis in free fatty acid-induced steatotic hepatocytes by inhibiting PINK1-mediated mitophagy, Inflammation 45 (2022) 639-650.
[45]	M.M. Sayed-Ahmed, M.M. Khattab, M.Z. Gad, et al., L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits, Pharmacol. Res. 44 (2001) 235-242.
[46]	R. Tabrizi, V. Ostadmohammadi, K.B. Lankarani, et al., The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials, Lipids Health Dis. 17 (2018), 123.
[47]	K. Sachin, S.K. Karn, Microbial fabricated nanosystems: Applications in drug delivery and targeting, Front. Chem. 9 (2021), 617353.
[48]	Y. Wang, Y. Xu, X. Xu, et al., Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism, Phytother. Res. 36 (2022) 2463-2480.
[49]	Z. Wang, B.A. Peters, M. Usyk, et al., Gut microbiota, plasma metabolomic profiles, and carotid artery atherosclerosis in HIV infection, Arterioscler. Thromb. Vasc. Biol. 42 (2022) 1081-1093.
[50]	T. Zhang, Q. Li, L. Cheng, et al., Akkermansia muciniphila is a promising probiotic, Microb. Biotechnol. 12 (2019) 1109-1125.
[51]	S. Sun, X. Xu, L. Liang, et al., Lactic acid-producing probiotic Saccharomyces cerevisiae attenuates ulcerative colitis via suppressing macrophage pyroptosis and modulating gut microbiota, Front. Immunol. 12 (2021), 777665.