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纳米药物治疗肝纤维化的研究进展

郭佳玲 李晖 曾子键 陶雨静 董海舰

引用本文:
Citation:

纳米药物治疗肝纤维化的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.02.026
基金项目: 

国家自然科学基金面上项目资助 (82274323)

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:郭佳玲负责撰写论文;曾子键、陶雨静、董海舰参与查找文献,修改论文;李晖负责拟定写作思路,指导文章撰写并最后定稿。
详细信息
    通信作者:

    李晖,1400124746@qq.com (ORCID: 0000-0002-5919-1396)

Research advances in nanomedicine in treatment of liver fibrosis

Research funding: 

National Natural Science Foundation of China (General Project) (82274323)

More Information
  • 摘要: 肝纤维化是由肝脏慢性损伤和炎症反应引起肝星状细胞(HSC)活化和细胞外基质过度沉积的病理过程。HSC活化是肝纤维化形成的核心机制,抑制HSC激活是促进肝纤维化逆转的关键。近年来,应用靶向HSC的纳米药物来治疗肝纤维化取得了快速发展。本文主要介绍纳米药物、纳米药物在肝纤维化中的作用机制及可能存在的潜在靶点。纳米药物有望成为治疗肝纤维化的新方法。

     

  • 表  1  已注册的部分纳米药物干预肝纤维化的临床试验

    Table  1.   Clinical trial of some registered nano drugs for intervention of liver fibrosis

    登记号 疾病 阶段 纳入人数 分配/盲法 干预模式 试验药物 靶点 开始时间/状态
    NCT02227459 肝纤维化、肝硬化 Ⅰ/Ⅱ 25 随机/开放标签 单组分配 ND-L02-s0201 SERPINH1 2014年10月/已完成
    NCT03142165 纤维化 I 33 随机/四人组(参与者、护理者、研究者、结果评估员) 平行分配 BMS-986263、法莫替丁、苯海拉明 SERPINH1、IFNAR、HRH2、HRH1 2017年5月/已完成
    NCT03241264 纤维化 I 12 随机/开放标签 交叉分配 ND-L02-s0201 SERPINH1 2016年8月/已完成
    NCT03420768 肝硬化、肝纤维化 61 随机/四人组(参与者、护理者、研究者、结果评估员) 平行分配 BMS-986263 SERPINH1 2018年2月/已完成
    NCT04225936 肝病 40 非随机/开放标签 顺序分配 BMS-986263 SERPINH1 2020年1月/已完成
    NCT04267393 非酒精性脂肪性肝炎、肝硬化 270 随机/四人组(参与者、护理者、研究者、结果评估员) 平行分配 BMS-986263 SERPINH1 2021年3月/进行中
    NCT04682847 肝硬化、肝癌等 - 25 _ _ 纳米氧化铁 _ 2020年11月/进行中
    注:ND-L02-s0201、BMS-986263,含有siRNA对抗HSP47的脂质纳米颗粒。
    下载: 导出CSV
  • [1] FAN J, TONG G, CHEN X, et al. CK2 blockade alleviates liver fibrosis by suppressing activation of hepatic stellate cells via the Hedgehog pathway[J]. Br J Pharmacol, 2023, 180(1): 44-61. DOI: 10.1111/bph.15945.
    [2] GU L, ZHANG F, WU J, et al. Nanotechnology in drug delivery for liver fibrosis[J]. Front Mol Biosci, 2021, 8: 804396. DOI: 10.3389/fmolb.2021.804396.
    [3] AHMED T, LIU FF, HE C, et al. Optimizing the design of blood-brain barrier-penetrating polymer-lipid-hybrid nanoparticles for delivering anticancer drugs to glioblastoma[J]. Pharm Res, 2021, 38(11): 1897-1914. DOI: 10.1007/s11095-021-03122-9.
    [4] DANAEI M, DEHGHANKHOLD M, ATAEI S, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems[J]. Pharmaceutics, 2018, 10(2): 57. DOI: 10.3390/pharmaceutics10020057.
    [5] YUAN S, ZHANG Q. Application of one-dimensional nanomaterials in catalysis at the single-molecule and single-particle scale[J]. Front Chem, 2021, 9: 812287. DOI: 10.3389/fchem.2021.812287.
    [6] KOERNER J, HORVATH D, GROETTRUP M. Harnessing dendritic cells for poly (D, L-lactide-co-glycolide) microspheres (PLGA MS)-mediated anti-tumor therapy[J]. Front Immunol, 2019, 10: 707. DOI: 10.3389/fimmu.2019.00707.
    [7] GIANNITRAPANI L, SORESI M, BONDÌ ML, et al. Nanotechnology applications for the therapy of liver fibrosis[J]. World J Gastroenterol, 2014, 20(23): 7242-7251. DOI: 10.3748/wjg.v20.i23.7242.
    [8] ZHANG A, MENG K, LIU Y, et al. Absorption, distribution, metabolism, and excretion of nanocarriers in vivo and their influences[J]. Adv Colloid Interface Sci, 2020, 284: 102261. DOI: 10.1016/j.cis.2020.102261.
    [9] ZHANG YN, POON W, TAVARES AJ, et al. Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination[J]. J Control Release, 2016, 240: 332-348. DOI: 10.1016/j.jconrel.2016.01.020.
    [10] BARTNECK M, WARZECHA KT, TACKE F. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine[J]. Hepatobiliary Surg Nutr, 2014, 3(6): 364-376. DOI: 10.3978/j.issn.2304-3881.2014.11.02.
    [11] PENG W, CHENG S, BAO Z, et al. Advances in the research of nanodrug delivery system for targeted treatment of liver fibrosis[J]. Biomed Pharmacother, 2021, 137: 111342. DOI: 10.1016/j.biopha.2021.111342.
    [12] SHEVTSOV M, ZHAO L, PROTZER U, et al. Applicability of metal nanoparticles in the detection and monitoring of hepatitis b virus infection[J]. Viruses, 2017, 9(7): 193. DOI: 10.3390/v9070193.
    [13] RIBERA J, VILCHES C, SANZ V, et al. Treatment of hepatic fibrosis in mice based on targeted plasmonic hyperthermia[J]. ACS Nano, 2021, 15(4): 7547-7562. DOI: 10.1021/acsnano.1c00988.
    [14] EL-BENDARY MA, AFIFI SS, MOHARAM ME, et al. Biosynthesis of silver nanoparticles using isolated Bacillus subtilis: characterization, antimicrobial activity, cytotoxicity, and their performance as antimicrobial agent for textile materials[J]. Prep Biochem Biotechnol, 2021, 51(1): 54-68. DOI: 10.1080/10826068.2020.1789992.
    [15] GAD SS, ABDELRAHIM DS, ISMAIL SH, et al. Selenium and silver nanoparticles: A new approach for treatment of bacterial and viral hepatic infections via modulating oxidative stress and DNA fragmentation[J]. J Biochem Mol Toxicol, 2022, 36(3): e22972. DOI: 10.1002/jbt.22972.
    [16] PENG F, TEE JK, SETYAWATI MI, et al. Inorganic nanomaterials as highly efficient inhibitors of cellular hepatic fibrosis[J]. ACS Appl Mater Interfaces, 2018, 10(38): 31938-31946. DOI: 10.1021/acsami.8b10527.
    [17] TEE JK, NG LY, KOH HY, et al. Titanium dioxide nanoparticles enhance leakiness and drug permeability in primary human hepatic sinusoidal endothelial cells[J]. Int J Mol Sci, 2018, 20(1): 35. DOI: 10.3390/ijms20010035.
    [18] KURNIAWAN DW, BOOIJINK R, PATER L, et al. Fibroblast growth factor 2 conjugated superparamagnetic iron oxide nanoparticles (FGF2-SPIONs) ameliorate hepatic stellate cells activation in vitro and acute liver injury in vivo[J]. J Control Release, 2020, 328: 640-652. DOI: 10.1016/j.jconrel.2020.09.041.
    [19] CORNU R, BÉDUNEAU A, MARTIN H. Influence of nanoparticles on liver tissue and hepatic functions: A review[J]. Toxicology, 2020, 430: 152344. DOI: 10.1016/j.tox.2019.152344.
    [20] GHARIEH A, KHOEE S, MAHDAVIAN AR. Emulsion and miniemulsion techniques in preparation of polymer nanoparticles with versatile characteristics[J]. Adv Colloid Interface Sci, 2019, 269: 152-186. DOI: 10.1016/j.cis.2019.04.010.
    [21] CHEN XF, JI S. Sorafenib attenuates fibrotic hepatic injury through mediating lysine crotonylation[J]. Drug Des Devel Ther, 2022, 16: 2133-2144. DOI: 10.2147/DDDT.S368306.
    [22] SUNG YC, LIU YC, CHAO PH, et al. Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development[J]. Theranostics, 2018, 8(4): 894-905. DOI: 10.7150/thno.21168.
    [23] LI M, DU C, GUO N, et al. Composition design and medical application of liposomes[J]. Eur J Med Chem, 2019, 164: 640-653. DOI: 10.1016/j.ejmech.2019.01.007.
    [24] ULLAH A, CHEN G, YIBANG Z, et al. A new approach based on CXCR4-targeted combination liposomes for the treatment of liver fibrosis[J]. Biomater Sci, 2022, 10(10): 2650-2664. DOI: 10.1039/d2bm00242f.
    [25] KESHARWANI SS, KAUR S, TUMMALA H, et al. Multifunctional approaches utilizing polymeric micelles to circumvent multidrug resistant tumors[J]. Colloids Surf B Biointerfaces, 2019, 173: 581-590. DOI: 10.1016/j.colsurfb.2018.10.022.
    [26] DOU JY, JIANG YC, HU ZH, et al. Betulin targets lipin1/2-meidated P2X7 receptor as a therapeutic approach to attenuate lipid accumulation and metaflammation[J]. Biomol Ther (Seoul), 2022, 30(3): 246-256. DOI: 10.4062/biomolther.2021.136.
    [27] XU J, WANG X, ZHANG H, et al. Synthesis of triterpenoid derivatives and their anti-tumor and anti-hepatic fibrosis activities[J]. Nat Prod Res, 2020, 34(6): 766-772. DOI: 10.1080/14786419.2018.1499642.
    [28] LIU XY, LI D, LI TY, et al. Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection[J]. Eur J Pharm Sci, 2022, 174: 106189. DOI: 10.1016/j.ejps.2022.106189.
    [29] BAI X, SU G, ZHAI S. Recent advances in nanomedicine for the diagnosis and therapy of liver fibrosis[J]. Nanomaterials (Basel), 2020, 10(10): 1945. DOI: 10.3390/nano10101945.
    [30] ZAVORKA ME, CONNELLY CM, GROSELY R, et al. Inhibition of insulin-like growth factor II (IGF-II)-dependent cell growth by multidentate pentamannosyl 6-phosphate-based ligands targeting the mannose 6-phosphate/IGF-II receptor[J]. Oncotarget, 2016, 7(38): 62386-62410. DOI: 10.18632/oncotarget.11493.
    [31] KUMAR V, MONDAL G, DUTTA R, et al. Co-delivery of small molecule hedgehog inhibitor and miRNA for treating liver fibrosis[J]. Biomaterials, 2016, 76: 144-156. DOI: 10.1016/j.biomaterials.2015.10.047.
    [32] LI F, LI QH, WANG JY, et al. Effects of interferon-gamma liposomes targeted to platelet-derived growth factor receptor-beta on hepatic fibrosis in rats[J]. J Control Release, 2012, 159(2): 261-270. DOI: 10.1016/j.jconrel.2011.12.023.
    [33] ZHANG J, SHEN H, XU J, et al. Liver-targeted siRNA lipid nanoparticles treat hepatic cirrhosis by dual antifibrotic and anti-inflammatory activities[J]. ACS Nano, 2020, 14(5): 6305-6322. DOI: 10.1021/acsnano.0c02633.
    [34] ZHENG Y, LEFTHERIS K. Insights into protein-ligand interactions in integrin complexes: advances in structure determinations[J]. J Med Chem, 2020, 63(11): 5675-5696. DOI: 10.1021/acs.jmedchem.9b01869.
    [35] XU T, LU Z, XIAO Z, et al. Myofibroblast induces hepatocyte-to-ductal metaplasia via laminin-ɑvβ6 integrin in liver fibrosis[J]. Cell Death Dis, 2020, 11(3): 199. DOI: 10.1038/s41419-020-2372-9.
    [36] KITSUGI K, NORITAKE H, MATSUMOTO M, et al. Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway[J]. Cell Signal, 2022, 99: 110437. DOI: 10.1016/j.cellsig.2022.110437.
    [37] ZHOU L, LI Y, LIANG Q, et al. Combination therapy based on targeted nano drug co-delivery systems for liver fibrosis treatment: a review[J]. J Drug Target, 2022, 30(6): 577-588. DOI: 10.1080/1061186X.2022.2044485.
    [38] EL-MEZAYEN NS, EL-HADIDY WF, EL-REFAIE WM, et al. Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence[J]. J Control Release, 2018, 283: 32-44. DOI: 10.1016/j.jconrel.2018.05.021.
    [39] CARRILLO-SEPULVEDA MA, KEEN HL, DAVIS DR, et al. Role of vascular smooth muscle PPARγ in regulating AT1 receptor signaling and angiotensin II-dependent hypertension[J]. PLoS One, 2014, 9(8): e103786. DOI: 10.1371/journal.pone.0103786.
    [40] UNO K, MIYAJIMA K, TOMA M, et al. CD44 expression in the bile duct epithelium is related to hepatic fibrosis in nonalcoholic steatohepatitis rats induced by a choline-deficient, methionine-lowered, L-amino acid diet[J]. J Toxicol Pathol, 2022, 35(2): 149-157. DOI: 10.1293/tox.2021-0069.
    [41] LUO J, ZHANG P, ZHAO T, et al. Golgi apparatus-targeted chondroitin-modified nanomicelles suppress hepatic stellate cell activation for the management of liver fibrosis[J]. ACS Nano, 2019, 13(4): 3910-3923. DOI: 10.1021/acsnano.8b06924.
    [42] LIANG H, LI Z, REN Z, et al. Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis[J]. Nano Research, 2020, 13(8): 2197-2202. DOI: 10.1007/s12274-020-2833-6.
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  • 收稿日期:  2022-11-03
  • 录用日期:  2022-12-05
  • 出版日期:  2023-02-20
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