摘要:急性肾损伤 (acute kidney injury,AKI) 是一种常见的与活性氧相关的肾脏疾病,往往伴随着肾脏功能 的急剧下降。此外,AKI经常增加慢性肾脏疾病和终末期肾病的风险。然而目前除了肾透析和肾移植,还没有特 定的治疗措施来治疗 AKI。纳米药物因其良好的物理化学特性,在生物医学中的应用越来越受到人们的关注。研 究在肾脏中具有高蓄积性的纳米药物有助于预防和治疗AKI。论文将纳米药物在AKI治疗应用方面的最新进展作 一综述。
图 1 纳米药物治疗 AKI 示意图
[1] LAMEIRE NH, BAGGA A, CRUZ D, et al. Acute kidney injury: an increasing global concern [J]. Lancet, 2013, 382(9887):170-179
[2] RONCO C, RICCI Z, DE BACKER D, et al. Renal replacement therapy in acute kidney injury: Controversyand consensus [J]. Crit Care, 2015,19(1):146
[3] PANNU N, MANNS B, LEE H, et al. Systematic review of the impact of N- acetylcysteine on contrast nephropathy [J]. Kidney Int, 2004,65(4):1366-1374
[4] ZHANG M, CHENG J, SUN Z, et al. Protective Effects of Carbon Dots Derived from Phellodendri Chinensis Cortex Carbonisata against Deinagkistrodon acutus Venom- Induced Acute Kidney Injury [J]. Nanoscale Res Lett, 2019, 14(1):377
[5] KHWAJA A. KDIGO clinical practice guidelines for acute kidney injury [J]. Nephron Clin Pract, 2012,120(4):c179- c184
[6] RONCO C, BELLOMO R, KELLUM JA. Acute kidney injury [J]. Lancet, 2019,394(10212):1949-1964
[7] DENNIS JM, WITTING PK. Protective role for antioxidants in acutekidney disease [J]. Nutrients, 2017,9(7):718
[8] KAUSHAL GP, CHANDRASHEKAR K, JUNCOS LA. Molecular interactionsbetween reactive oxygen species and autophagy in kidney disease [J]. Int J Mol Sci, 2019,20 (15):3791
[9] PANIZO N, RUBIO- NAVARRO A, AMARO- VILLALOBOS JM, et al. Molecular mechanisms and novel therapeutic approachesto rhabdomyolysis-induced acute kidney injury [J]. Kidney Blood Press Res, 2015,40(5):520- 532
[10] SINGH P, KESHARWANI RK, KESERVANI RK. 24- antioxidants andvitamins: Roles in cellular function and metabolism[M/OL]//In SustainedEnergy for Enhanced Human Functions and Activity, Publisher: Andre G. Wolff, 2017,385-407
[11] MATOUGH FA, BUDIN SB, HAMID ZA, et al. The role of oxidative stress and antioxidants in diabetic complications[J]. Sultan Qaboos Univ Med J, 2012,12(1):5-18
[12] FIRUZI O, MIRI R, TAVAKKOLI M, et al. Antioxidant therapy: Current status and future prospects [J]. Curr Med Chem, 2011,18(25):3871-3888
[13] YU M, XU J, ZHENG J. Renal clearable luminescent gold nanoparticles: From the bench to the clinic [J]. Angew Chem Int Ed Engl, 2019,58(13):4112-4128.[14] MIN Y, CASTER JM, EBLAN MJ, et al. Clinical translation of nanomedicine [J]. Chem Rev, 2015,115(19): 11147-11190
[15] PELAZ B, ALEXIOU C, ALVAREZ- PUEBLA RA, et al. Diverse applications of nanomedicine [J]. ACS Nano, 2017,11(3):2313-2381
[16] LIU D, JIN F, SHU G, et al. Enhanced efficiency ofmitochondria- targeted peptide SS- 31 for acute kidney injury bypH- responsive and AKI- kidney targeted nanopolyplexes [J]. Biomaterials, 2019,211:57-67
[17] ZENG YP, ZENG WN, ZHOU Q, et al. Hyaluronic acid mediated biomineralization of multifunctional ceria nanocomposites as ROS scavengers andtumor photodynamic therapy agents [J]. J Mater Chem B, 2019,7(20):3210- 3219
[18] AWAD AS, EL- SHARIF AA. Curcumin immune- mediated and anti- apoptotic mechanisms protect against renal ischemia/reperfusionand distant organ induced injuries [J]. Int Immunopharmacol, 2011,11(8):992-996
[19] ALLIJN IE, SCHIFFELERS RM, STORM G. Comparison ofpharmaceutical nanoformulations for curcumin: Enhancement ofaqueous solubility and carrier retention [J]. Int J Pharm, 2016,506(1-2):407-413
[20] HU JB, LI SJ, KANG XQ, et al. CD44- targeted hyaluronic acid- curcumin prodrug protects renal tubular epithelialcell survival from oxidative stress damage [J]. Carbohydr Polym, 2018,193:268-280
[21] HOLTHOFF JH, WANG Z, SEELY KA. Resveratrol improves renal microcirculation, protects the tubularepithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury [J]. Kidney Int, 2012,81(4):370- 378
[22] ZHANG R, YIN L, ZHANG B, et al. Resveratrol improveshuman umbilical cord- derived mesenchymal stem cells repair forcisplatin- induced acute kidney injury [J]. Cell Death Dis, 2018,9(10):965
[23] SUMMERLIN N, SOO E, THAKUR S. Resveratrol nanoformulations: Challenges and opportunities [J]. Int J Pharm, 2015,479(2):282-290
[24] HAN WK, BAILLY V, Abichandani R. Kidney injury molecule- 1 (KIM- 1): A novel biomarker forhuman renal proximal tubule injury [J]. Kidney Int, 2002,62(1):237-244
[25] LIN YF, LEE YH, HSU YH, et al. Resveratrol- loaded nanoparticles conjugated withkidney injury molecule- 1 as a drug delivery system for potentialuse in chronic kidney disease [J]. Nanomedicine, 2017,12(22):2741-2756
[26] NI D, JIANG D, KUTYREFF CJ, et al. Molybdenumbased nanoclusters act as antioxidants and ameliorate acute kidneyinjury in mice [J]. Nat Commun, 2018,9(1):5421
[27] KWON HJ, KIM D, SEO K, et al. Ceria nanoparticle systems for selective scavengingof mitochondrial, intracellular, and extracellular reactive oxygenspecies in parkinson's disease [J]. Angew Chem Int Ed, 2018,57(30):9408-9412
[28] YU H, JIN F, LIU D, et al. ROS- responsive nanodrugdelivery system combining mitochondria- targeting ceria nanoparticleswith atorvastatin for acute kidney injury [J]. Theranostics, 2020,10(5):2342-2357
[29] HAHN J, WICKHAM SF, SHIH WM. Addressingthe instability of DNA nanostructures in tissue culture [J]. ACS Nano, 2014,8(9):8765-8775
[30] DU Y, JIANG Q, BEZIERE N, et al. DNA- nanostructure-gold-nanorod hybrids for enhanced in vivo optoacoustic imagingand photothermal therapy [J]. Adv Mater, 2016, 28(45):10000-10007
[31] MATTER B, SEILER CL, MURPHY K, et al. Mapping three guanineoxidation products along DNA following exposure to three typesof reactive oxygen species [J]. Free Radic Biol Med, 2018,121:180-189
[32] JIANG D, GE Z, IM HJ, et al. DNA origaminanostructures can exhibit preferential renal uptake and alleviateacute kidney injury [J]. Nat Biomed Eng, 2018,2(11):865-877
[33] SHAO J, XIE H, HUANG H, et al. Biodegradable black phosphorus- based nanospheres for in vivo photothermalcancer therapy [J]. Nat Commun, 2016,7(1):12967
[34] HOU J, WANG H, GE Z, et al. Treating acute kidneyinjury with antioxidative black phosphorus nanosheets[J]. Nano Lett, 2020,20(2):1447-1454
[35] PARK SM, AALIPOUR A, VERMESH, O, et al. Towards clinically translatable in vivo nanodiagnostics [J]. Nat Rev Mater, 2017,2(5):17014.
张道富,毕罗鹏,王艳波. 抗氧化纳米药物治疗急性肾损伤的研究进展[J]. 泌尿外科杂志(电子版),2021,13(2):81-84. DOI:10.3969/j.issn.1674-7410.2021.02.018.
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急性肾损伤 (acute kidney injury,AKI) 也称 急性肾衰竭,是由多种病因导致的急性肾小球滤过 率下降,以血肌酐增高及尿量减少为主要临床表现 的疾病,具有较高的发病率和死亡率[1] 。目前针对 AKI的治疗仍以早期液体复苏或肾脏替代治疗等干 预为主,缺乏有效的药物治疗手段[2] 。抗氧化剂 N- 乙酰半胱氨酸 (N-acetylcysteine,NAC) 在预防造 影剂导致的 AKI方面取得了一定的成功,但应用该 药的利弊问题仍值得商榷[3] 。
纳米药物在生物医学中的应用越来越受到人们 的关注,在过去的几十年里,纳米医学在各种疾病 的成像和治疗方面取得了长足进步[4] ,这一进展将促 进 AKI 评估与治疗的进步。本文对纳米药物治疗 AKI的研究进展作一综述。
1 AKI 的诊断标准
2 AKI 的发病机制
3 治疗 AKI 的常用抗氧化剂
4 治疗 AKI 的纳米药物
4.1 肾靶向的纳米药物
4.2 具有高肾摄取性的金属抗氧化纳米簇
4.3 DNA 折纸结构
4.4 黑磷纳米片
5 结语与展望
5 结语与展望
近年来,纳米药物因其具有非常大的生物医学 应用前景受到研究人员越来越多的关注,不仅在肿 瘤的早期诊断和治疗,而且在 AKI以及 ROS的相关 疾病中均有显著的治疗效果。提高纳米药物的肾靶 向效率是一个非常重要的研究方面。例如,研究表明 用聚乙二醇 PEG包封 DNA折纸结构可以提高它们的 药代生物学利用度,进而延长肾靶向时间窗。简单 的改变可以有效保护 DNA 折纸结构,免于受血液中 蛋白酶的降解和变性[32] 。未来的研究还要继续关注纳 米粒子的形态、尺寸和表面修饰对肾靶向性的影响。
然而,目前纳米医学的研究主要集中在动物模 型,动物模型虽然可以模拟人类的一些疾病,但在 研究纳米药物的药代动力学时必须将种间差异考虑 进去。另外,纳米粒子在人体中的生物分布较难评 估。因此,从实验室到临床的创新过程仍需要努 力,临床前和临床模型之间的差异在纳米药物的发 展中也应该被仔细考虑。目前,纳米药物在 AKI治 疗中的应用尚处于起步阶段,其毒性、靶向性、清除机制尚不清楚[35] 。相信在不久的将来这些问题会得 到阐明,AKI将会得到更精准、更科学、更安全的治疗。
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