不同药物载体靶向治疗动脉粥样硬化
Different Drug Carriers Targeted for Atherosclerosis Treatment
DOI: 10.12677/acm.2025.152494, PDF,   
作者: 周若愚*, 宋佳琪, 詹晓丹, 贺 娜, 刘增长#:重庆医科大学附属第二医院心内科,重庆
关键词: 靶向动脉粥样硬化载体Targeting Atherosclerosis Carriers
摘要: 动脉粥样硬化是一种慢性进行性炎症性血管疾病,是许多心脑血管疾病发展的重要病理基础。传统的药物治疗和介入或手术治疗效果不佳,且有严重的并发症。尽管已经研究了多种抗动脉粥样硬化的靶物质,但如何将这些物质准确地递送到受损的血管内皮并保持其生物活性是一个重大挑战。最近的研究表明,合适的载体可以更好地解决这些问题,从而提供更安全,更有效和更具成本效益的治疗策略。
Abstract: Atherosclerosis is a chronic progressive inflammatory vascular disease that is an important pathological basis for the development of many cardiovascular diseases. Traditional pharmacological treatments and interventional or surgical treatments are ineffective and have serious complications. Although a variety of anti-atherosclerotic target substances have been investigated, it is a major challenge to accurately deliver these substances to the damaged vascular endothelium and to maintain their biological activity. Recent studies have shown that suitable carriers can better address these issues, thus providing safer, more effective and cost-efficient therapeutic strategies.
文章引用:周若愚, 宋佳琪, 詹晓丹, 贺娜, 刘增长. 不同药物载体靶向治疗动脉粥样硬化[J]. 临床医学进展, 2025, 15(2): 1441-1450. https://doi.org/10.12677/acm.2025.152494

参考文献

[1] Jebari-Benslaiman, S., Galicia-García, U., Larrea-Sebal, A., Olaetxea, J.R., Alloza, I., Vandenbroeck, K., et al. (2022) Pathophysiology of Atherosclerosis. International Journal of Molecular Sciences, 23, Article 3346. [Google Scholar] [CrossRef] [PubMed]
[2] Björkegren, J.L.M. and Lusis, A.J. (2022) Atherosclerosis: Recent Developments. Cell, 185, 1630-1645. [Google Scholar] [CrossRef] [PubMed]
[3] Golforoush, P., Yellon, D.M. and Davidson, S.M. (2020) Mouse Models of Atherosclerosis and Their Suitability for the Study of Myocardial Infarction. Basic Research in Cardiology, 115, Article No. 73. [Google Scholar] [CrossRef] [PubMed]
[4] Ji, E. and Lee, S. (2021) Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases. International Journal of Molecular Sciences, 22, Article 5770. [Google Scholar] [CrossRef] [PubMed]
[5] Zhu, Z. and Yu, W. (2020) Update in the Treatment of Extracranial Atherosclerotic Disease for Stroke Prevention. Stroke and Vascular Neurology, 5, 65-70.
[6] Bergami, M., Cenko, E., Yoon, J., Mendieta, G., Kedev, S., Zdravkovic, M., et al. (2021) Statins for Primary Prevention among Elderly Men and Women. Cardiovascular Research, 118, 3000-3009. [Google Scholar] [CrossRef] [PubMed]
[7] Al-Abdouh, A., Abusnina, W., Mhanna, M., Radideh, Q., Alzu’bi, H., Rmilah, A.A., et al. (2022) P2Y12 Inhibitors versus Aspirin Monotherapy for Long-Term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-Analysis. Current Problems in Cardiology, 47, Article 101292. [Google Scholar] [CrossRef] [PubMed]
[8] Lovren, F., Pan, Y., Quan, A., Singh, K.K., Shukla, P.C., Gupta, N., et al. (2012) MicroRNA-145 Targeted Therapy Reduces Atherosclerosis. Circulation, 126, S81-S90. [Google Scholar] [CrossRef] [PubMed]
[9] Almeida, S.O. and Budoff, M. (2019) Effect of Statins on Atherosclerotic Plaque. Trends in Cardiovascular Medicine, 29, 451-455. [Google Scholar] [CrossRef] [PubMed]
[10] Attardo, S., Musumeci, O., Velardo, D. and Toscano, A. (2022) Statins Neuromuscular Adverse Effects. International Journal of Molecular Sciences, 23, Article 8364. [Google Scholar] [CrossRef] [PubMed]
[11] Lamprecht, D.G., Saseen, J.J. and Shaw, P.B. (2022) Clinical Conundrums Involving Statin Drug-Drug Interactions. Progress in Cardiovascular Diseases, 75, 83-89. [Google Scholar] [CrossRef] [PubMed]
[12] Björnsson, E., Jacobsen, E.I. and Kalaitzakis, E. (2012) Hepatotoxicity Associated with Statins: Reports of Idiosyncratic Liver Injury Post-Marketing. Journal of Hepatology, 56, 374-380. [Google Scholar] [CrossRef] [PubMed]
[13] Averbukh, L.D., Turshudzhyan, A., Wu, D.C. and Wu, G.Y. (2022) Statin-Induced Liver Injury Patterns: A Clinical Review. Journal of Clinical and Translational Hepatology, 10, 543-552. [Google Scholar] [CrossRef] [PubMed]
[14] Liu, A., Wu, Q., Guo, J., Ares, I., Rodríguez, J., Martínez-Larrañaga, M., et al. (2019) Statins: Adverse Reactions, Oxidative Stress and Metabolic Interactions. Pharmacology & Therapeutics, 195, 54-84. [Google Scholar] [CrossRef] [PubMed]
[15] Mora, S., Shufelt, C.L. and Manson, J.E. (2022) Whom to Treat for Primary Prevention of Atherosclerotic Cardiovascular Disease: The Aspirin Dilemma. JAMA Internal Medicine, 182, 587-589. [Google Scholar] [CrossRef] [PubMed]
[16] Borovac, J.A., D’Amario, D., Vergallo, R., Porto, I., Bisignani, A., Galli, M., et al. (2018) Neoatherosclerosis after Drug-Eluting Stent Implantation: A Novel Clinical and Therapeutic Challenge. European Heart Journal-Cardiovascular Pharmacotherapy, 5, 105-116. [Google Scholar] [CrossRef] [PubMed]
[17] Colin, S., Chinetti‐Gbaguidi, G. and Staels, B. (2014) Macrophage Phenotypes in Atherosclerosis. Immunological Reviews, 262, 153-166. [Google Scholar] [CrossRef] [PubMed]
[18] Chinetti-Gbaguidi, G., Colin, S. and Staels, B. (2014) Macrophage Subsets in Atherosclerosis. Nature Reviews Cardiology, 12, 10-17. [Google Scholar] [CrossRef] [PubMed]
[19] Schulz, C. and Massberg, S. (2014) Atherosclerosis—Multiple Pathways to Lesional Macrophages. Science Translational Medicine, 6, 239ps2. [Google Scholar] [CrossRef] [PubMed]
[20] Tang, J., Lobatto, M.E., Hassing, L., van der Staay, S., van Rijs, S.M., Calcagno, C., et al. (2015) Inhibiting Macrophage Proliferation Suppresses Atherosclerotic Plaque Inflammation. Science Advances, 1, e1400223. [Google Scholar] [CrossRef] [PubMed]
[21] Bhaskar, S., Sudhakaran, P.R. and Helen, A. (2016) Quercetin Attenuates Atherosclerotic Inflammation and Adhesion Molecule Expression by Modulating TLR-NF-κB Signaling Pathway. Cellular Immunology, 310, 131-140. [Google Scholar] [CrossRef] [PubMed]
[22] Gao, C., Liu, C., Chen, Q., Wang, Y., Kwong, C.H.T., Wang, Q., et al. (2022) Cyclodextrin-Mediated Conjugation of Macrophage and Liposomes for Treatment of Atherosclerosis. Journal of Controlled Release, 349, 2-15. [Google Scholar] [CrossRef] [PubMed]
[23] Wang, Y., Zhang, K., Li, T., Maruf, A., Qin, X., Luo, L., et al. (2021) Macrophage Membrane Functionalized Biomimetic Nanoparticles for Targeted Anti-Atherosclerosis Applications. Theranostics, 11, 164-180. [Google Scholar] [CrossRef] [PubMed]
[24] Gao, C., Huang, Q., Liu, C., Kwong, C.H.T., Yue, L., Wan, J., et al. (2020) Treatment of Atherosclerosis by Macrophage-Biomimetic Nanoparticles via Targeted Pharmacotherapy and Sequestration of Proinflammatory Cytokines. Nature Communications, 11, Article No. 2622. [Google Scholar] [CrossRef] [PubMed]
[25] Burn, G.L., Foti, A., Marsman, G., Patel, D.F. and Zychlinsky, A. (2021) The Neutrophil. Immunity, 54, 1377-1391. [Google Scholar] [CrossRef] [PubMed]
[26] Liu, C., Jiang, Z., Pan, Z. and Yang, L. (2022) The Function, Regulation and Mechanism of Programmed Cell Death of Macrophages in Atherosclerosis. Frontiers in Cell and Developmental Biology, 9, Article 809516. [Google Scholar] [CrossRef] [PubMed]
[27] Bot, I., Shi, G. and Kovanen, P.T. (2015) Mast Cells as Effectors in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 35, 265-271. [Google Scholar] [CrossRef] [PubMed]
[28] Drechsler, M., Megens, R.T.A., van Zandvoort, M., Weber, C. and Soehnlein, O. (2010) Hyperlipidemia-Triggered Neutrophilia Promotes Early Atherosclerosis. Circulation, 122, 1837-1845. [Google Scholar] [CrossRef] [PubMed]
[29] Leclercq, A., Houard, X., Philippe, M., Ollivier, V., Sebbag, U., Meilhac, O., et al. (2007) Involvement of Intraplaque Hemorrhage in Atherothrombosis Evolution via Neutrophil Protease Enrichment. Journal of Leukocyte Biology, 82, 1420-1429. [Google Scholar] [CrossRef] [PubMed]
[30] Williams, M.R., Azcutia, V., Newton, G., Alcaide, P. and Luscinskas, F.W. (2011) Emerging Mechanisms of Neutrophil Recruitment across Endothelium. Trends in Immunology, 32, 461-469. [Google Scholar] [CrossRef] [PubMed]
[31] Kolaczkowska, E. and Kubes, P. (2013) Neutrophil Recruitment and Function in Health and Inflammation. Nature Reviews Immunology, 13, 159-175. [Google Scholar] [CrossRef] [PubMed]
[32] Soehnlein, O. (2012) Multiple Roles for Neutrophils in Atherosclerosis. Circulation Research, 110, 875-888. [Google Scholar] [CrossRef] [PubMed]
[33] Xue, Y., Wu, Y., Wang, Q., Xue, L., Su, Z. and Zhang, C. (2019) Cellular Vehicles Based on Neutrophils Enable Targeting of Atherosclerosis. Molecular Pharmaceutics, 16, 3109-3120. [Google Scholar] [CrossRef] [PubMed]
[34] Eulalio, A., Mano, M., Ferro, M.D., Zentilin, L., Sinagra, G., Zacchigna, S., et al. (2012) Functional Screening Identifies Mirnas Inducing Cardiac Regeneration. Nature, 492, 376-381. [Google Scholar] [CrossRef] [PubMed]
[35] Giacca, M. and Zacchigna, S. (2015) Harnessing the MicroRNA Pathway for Cardiac Regeneration. Journal of Molecular and Cellular Cardiology, 89, 68-74. [Google Scholar] [CrossRef] [PubMed]
[36] Fernandez-Piñeiro, I., Badiola, I. and Sanchez, A. (2017) Nanocarriers for MicroRNA Delivery in Cancer Medicine. Biotechnology Advances, 35, 350-360. [Google Scholar] [CrossRef] [PubMed]
[37] 忻锦霞. 仿生中性粒细胞纳米囊泡靶向递送miR-199a-3p治疗心肌梗死[D]: [硕士学位论文]. 杭州: 浙江大学医学院, 2021.
[38] Kooiman, K., Foppen-Harteveld, M., van der Steen, A.F.W. and de Jong, N. (2011) Sonoporation of Endothelial Cells by Vibrating Targeted Microbubbles. Journal of Controlled Release, 154, 35-41. [Google Scholar] [CrossRef] [PubMed]
[39] Ullah, M., Kodam, S.P., Mu, Q. and Akbar, A. (2021) Microbubbles versus Extracellular Vesicles as Therapeutic Cargo for Targeting Drug Delivery. ACS Nano, 15, 3612-3620. [Google Scholar] [CrossRef] [PubMed]
[40] Liu, F., Mao, Y., Yan, J., Sun, Y., Xie, Z., Li, F., et al. (2022) Bionic Microbubble Neutrophil Composite for Inflammation-Responsive Atherosclerotic Vulnerable Plaque Pluripotent Intervention. Research, 2022, Article ID: 9830627. [Google Scholar] [CrossRef] [PubMed]
[41] Hemmat, N., Ebadi, A., Badalzadeh, R., Memar, M.Y. and Baghi, H.B. (2018) Viral Infection and Atherosclerosis. European Journal of Clinical Microbiology & Infectious Diseases, 37, 2225-2233. [Google Scholar] [CrossRef] [PubMed]
[42] Rauff, B., Malik, A., Bhatti, Y.A., Chudhary, S.A., Fatima, K., Rafiq, S., et al. (2021) Association of Viruses in the Development of Cardiovascular Diseases. Current Pharmaceutical Design, 27, 3913-3923. [Google Scholar] [CrossRef] [PubMed]
[43] Ison, M.G. and Hayden, R.T. (2016) Adenovirus. Microbiology Spectrum, 4. [Google Scholar] [CrossRef] [PubMed]
[44] Gallardo, J., Pérez-Illana, M., Martín-González, N. and San Martín, C. (2021) Adenovirus Structure: What Is New? International Journal of Molecular Sciences, 22, Article 5240. [Google Scholar] [CrossRef] [PubMed]
[45] Arnberg, N. (2012) Adenovirus Receptors: Implications for Targeting of Viral Vectors. Trends in Pharmacological Sciences, 33, 442-448. [Google Scholar] [CrossRef] [PubMed]
[46] Douglas, J. and Curiel, D. (1997) Targeted Adenoviral Vectors for Cancer Gene Therapy (Review). International Journal of Oncology, 11, 341-348. [Google Scholar] [CrossRef] [PubMed]
[47] Shan, L., Cui, S., Du, C., Wan, S., Qian, Z., Achilefu, S., et al. (2012) A Paclitaxel-Conjugated Adenovirus Vector for Targeted Drug Delivery for Tumor Therapy. Biomaterials, 33, 146-162. [Google Scholar] [CrossRef] [PubMed]
[48] Sasaki, T., Tazawa, H., Hasei, J., Osaki, S., Kunisada, T., Yoshida, A., et al. (2012) A Simple Detection System for Adenovirus Receptor Expression Using a Telomerase-Specific Replication-Competent Adenovirus. Gene Therapy, 20, 112-118. [Google Scholar] [CrossRef] [PubMed]
[49] Toivonen, R., Mäyränpää, M.I., Kovanen, P.T. and Savontaus, M. (2009) Dilated Cardiomyopathy Alters the Expression Patterns of CAR and Other Adenoviral Receptors in Human Heart. Histochemistry and Cell Biology, 133, 349-357. [Google Scholar] [CrossRef] [PubMed]
[50] Tomko, R.P., Xu, R. and Philipson, L. (1997) HCAR and MCAR: The Human and Mouse Cellular Receptors for Subgroup C Adenoviruses and Group B Coxsackieviruses. Proceedings of the National Academy of Sciences, 94, 3352-3356. [Google Scholar] [CrossRef] [PubMed]
[51] Tang, C., Liu, Y., Kessler, P.S., Vaughan, A.M. and Oram, J.F. (2009) The Macrophage Cholesterol Exporter ABCA1 Functions as an Anti-Inflammatory Receptor. Journal of Biological Chemistry, 284, 32336-32343. [Google Scholar] [CrossRef] [PubMed]
[52] Millar, J.S. and Cuchel, M. (2015) ApoA-I-Directed Therapies for the Management of Atherosclerosis. Current Atherosclerosis Reports, 17, Article No. 60. [Google Scholar] [CrossRef] [PubMed]
[53] Schwartze, J.T., Havenga, M., Bakker, W.A.M., Bradshaw, A.C. and Nicklin, S.A. (2022) Adenoviral Vectors for Cardiovascular Gene Therapy Applications: A Clinical and Industry Perspective. Journal of Molecular Medicine, 100, 875-901. [Google Scholar] [CrossRef] [PubMed]
[54] Flynn, R., Buckler, J.M., Tang, C., Kim, F. and Dichek, D.A. (2010) Helper-Dependent Adenoviral Vectors Are Superior in vitro to First-Generation Vectors for Endothelial Cell-Targeted Gene Therapy. Molecular Therapy, 18, 2121-2129. [Google Scholar] [CrossRef] [PubMed]
[55] Zinn, E. and Vandenberghe, L.H. (2014) Adeno-Associated Virus: Fit to Serve. Current Opinion in Virology, 8, 90-97. [Google Scholar] [CrossRef] [PubMed]
[56] Skubis-Zegadło, J., Stachurska, A. and Małecki, M. (2013) Vectrology of Adeno-Associated Viruses (AAV). Medycyna Wieku Rozwo-Jowego, 17, 202-206.
[57] Bish, L.T., Sweeney, H.L., Müller, O.J. and Bekeredjian, R. (2011) Adeno-Associated Virus Vector Delivery to the Heart. In: Snyder, R. and Moullier, P., Eds., Methods in Molecular Biology, Humana Press, 219-237. [Google Scholar] [CrossRef] [PubMed]
[58] Nayerossadat, N., Maedeh, T. and Ali, P. (2012) Viral and Nonviral Delivery Systems for Gene Delivery. Advanced Biomedical Research, 1, 27. [Google Scholar] [CrossRef] [PubMed]
[59] Katz, M.G., Fargnoli, A.S., Williams, R.D. and Bridges, C.R. (2013) Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications. Human Gene Therapy, 24, 914-927. [Google Scholar] [CrossRef] [PubMed]
[60] Thaci, B., Ulasov, I.V., Wainwright, D.A. and Lesniak, M.S. (2011) The Challenge for Gene Therapy: Innate Immune Response to Adenoviruses. Oncotarget, 2, 113-121. [Google Scholar] [CrossRef] [PubMed]
[61] 冯辰昀, 李旭东, 郑妤婕, 刘慧, 龚夏丹, 高瑜. 纳米材料的毒理学研究进展[J]. 中国科学(化学), 2022, 52(1): 15-22.
[62] Oberdörster, G. (2009) Safety Assessment for Nanotechnology and Nanomedicine: Concepts of Nanotoxicology. Journal of Internal Medicine, 267, 89-105. [Google Scholar] [CrossRef] [PubMed]
[63] Lu, Y., Thavarajah, T., Gu, W., Cai, J. and Xu, Q. (2018) Impact of miRNA in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 38, e159-e170. [Google Scholar] [CrossRef] [PubMed]
[64] Leal, B.H., Velasco, B., Cambón, A., Pardo, A., Fernandez-Vega, J., Arellano, L., et al. (2022) Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors. Pharmaceutics, 14, Article 258. [Google Scholar] [CrossRef] [PubMed]
[65] Allen, S.D., Liu, Y., Kim, T., Bobbala, S., Yi, S., Zhang, X., et al. (2019) Celastrol-Loaded PEG-b-PPS Nanocarriers as an Anti-Inflammatory Treatment for Atherosclerosis. Biomaterials Science, 7, 657-668. [Google Scholar] [CrossRef] [PubMed]
[66] Kojima, Y., Volkmer, J., McKenna, K., Civelek, M., Lusis, A.J., Miller, C.L., et al. (2016) CD47-Blocking Antibodies Restore Phagocytosis and Prevent Atherosclerosis. Nature, 536, 86-90. [Google Scholar] [CrossRef] [PubMed]
[67] Chen, L., Zhou, Z., Hu, C., Maitz, M.F., Yang, L., Luo, R., et al. (2022) Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy. Research, 2022, Article ID: 9845459. [Google Scholar] [CrossRef] [PubMed]
[68] Bourquin, J., Milosevic, A., Hauser, D., Lehner, R., Blank, F., Petri‐Fink, A., et al. (2018) Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials. Advanced Materials, 30, Article ID: 1704307. [Google Scholar] [CrossRef] [PubMed]
[69] Moyano, D.F., Liu, Y., Peer, D. and Rotello, V.M. (2015) Modulation of Immune Response Using Engineered Nanoparticle Surfaces. Small, 12, 76-82. [Google Scholar] [CrossRef] [PubMed]
[70] Mo, J., Xie, Q., Wei, W. and Zhao, J. (2018) Revealing the Immune Perturbation of Black Phosphorus Nanomaterials to Macrophages by Understanding the Protein Corona. Nature Communications, 9, Article No. 2480. [Google Scholar] [CrossRef] [PubMed]
[71] Sharifi, S., Behzadi, S., Laurent, S., Laird Forrest, M., Stroeve, P. and Mahmoudi, M. (2012) Toxicity of Nanomaterials. Chemical Society Reviews, 41, 2323-2343. [Google Scholar] [CrossRef] [PubMed]
[72] Wu, D., Ma, Y., Cao, Y. and Zhang, T. (2020) Mitochondrial Toxicity of Nanomaterials. Science of the Total Environment, 702, Article 134994. [Google Scholar] [CrossRef] [PubMed]
[73] Fan, G., Fan, M., Wang, Q., Jiang, J., Wan, Y., Gong, T., et al. (2016) Bio-Inspired Polymer Envelopes around Adenoviral Vectors to Reduce Immunogenicity and Improve in Vivo Kinetics. Acta Biomaterialia, 30, 94-105. [Google Scholar] [CrossRef] [PubMed]
[74] Kreppel, F. and Hagedorn, C. (2021) Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors. International Journal of Molecular Sciences, 22, Article 2417. [Google Scholar] [CrossRef] [PubMed]