[1]王华伟,张宇睿,徐文清.线粒体靶向药物的研究进展[J].国际放射医学核医学杂志,2016,40(4):312-317.[doi:10.3760/cma.j.issn.1673-4114.2016.04.015]
 Wang Huawei,Zhang Yurui,Xu Wenqing.Progress in mitochondrial targeting drug delivery systems[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(4):312-317.[doi:10.3760/cma.j.issn.1673-4114.2016.04.015]
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
40
期数:
2016年第4期
页码:
312-317
栏目:
出版日期:
2016-07-25

文章信息/Info

Title:
Progress in mitochondrial targeting drug delivery systems
作者:
王华伟 张宇睿 徐文清
300192 天津, 中国医学科学院北京协和医学院放射医学研究所, 天津市放射医学与分子核医学重点实验室
Author(s):
Wang Huawei Zhang Yurui Xu Wenqing
Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
关键词:
线粒体靶向治疗给药系统线粒体疾病辐射防护剂
Keywords:
MitochondriaTargeted therapyMedication systemMitochondrial diseasesRadiation-protective agents
DOI:
10.3760/cma.j.issn.1673-4114.2016.04.015
摘要:
电离辐射产生的活性氧(ROS)和自由基攻击DNA、脂质、蛋白质等生物大分子,造成机体细胞和组织的损伤。体内ROS主要来自线粒体,辐射造成线粒体损伤,使细胞内ROS持续增加。线粒体靶向抗氧化剂由于靶向在线粒体释放,能够高效地消除辐射导致的线粒体内过量ROS,保护线粒体,降低电离辐射对细胞的损伤,被认为是一类有前景的辐射损伤防护药。近年来,文献报道了多种线粒体靶向给药系统,笔者主要分析了线粒体靶向给药系统的方法及其发展趋势以及在辐射防护上的应用潜能。
Abstract:
Free radicals and reactive oxygen species(ROS) generated by ionizing radiation attack vital macromolecules, such as DNA, lipids and Proteins ,thus causing cell and tissue damage. The major source of radiation-induced ROS production is believed to be associated with mitochondria. Removal of excessive mitochondrial reactive oxygen species by electron scavengers and antioxidants is a promising therapeutic strategy to reduce the detrimental effects of radiation exposure. Mitochondrial targeting antioxidants and electron scavengers have been suggested as promising radioprotectors due to their well ability to remove of excessive mitochondrial reactive oxygen species. Papers about mitochondrial targeting drug delivery systems have been publicated in recent years. Technique of mitochondrial targeting drug delivery system, potential application in radiation protection and its development trend are discussed in this review.

参考文献/References:

[1] Chan DC.Mitochondria:dynamic organelles in disease, aging, and development[J].Cell, 2006, 125(7):1241-1252.DOI:10.1016/j.cell.2006.06.010.
[2] Heller A, Brockhoff G, Goepferich A.Targeting drugs to mitochondria[J].Eur J Pharm Biopharm, 2012, 82(1):1-18.DOI:10.1016/j.ejpb.2012.05.014.
[3] D’Souza GG, Wagle MA, Saxena V, et al.Approaches for targeting mitochondria in cancer therapy[J].Biochim Biophys Acta, 2011, 1807(6):689-696.DOI:10.1016/j.bbabio.2010.08.008.
[4] Rwigema JC, Beck B, Wang W, et al.Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators[J].Int J Radiat Oncol Biol Phys, 2011, 80(3):860-868.DOI:10.1016/j.ijrobp.2011.01.059.
[5] Jiang J, Stoyanovsky DA, Belikova NA, et al.A mitochondria-targeted triphenylphosphonium-conjugated nitroxide functions as a radioprotector/mitigator[J].Radiat Res, 2009, 172(6):706-717.DOI:10.1667/RR1729.1.
[6] Zhou J, Zhao WY, Ma X, et al.The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate in resistant lung cancer[J].Biomaterials, 2013, 34(14):3626-3638.DOI:10.1016/j.biomaterials.2013.01.078.
[7] Reily C, Mitchell T, Chacko BK, et al.Mitochondrially targeted compounds and their impact on cellular bioenergetics[J].Redox Biol, 2013, 1(1):86-93.DOI:10.1016/j.redox.2012.11.009.
[8] Mao P, Manczak M, Shirendeb UP, et al.MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis[J].Biochim Biophys Acta, 2013, 1832(12):2322-2331.DOI:10.1016/j.bbadis.2013.09.005.
[9] Milagros RM, Victor VM.Targeting antioxidants to mitochondria and cardiovascular diseases:the effects of mitoquinone[J].Med Sci Monit, 2007, 13(7):RA132-145.
[10] Li L, Brichard L, Larsen L, et al.Radiosynthesis of 11-(18F) fluoroundecyltriphenylphosphonium(MitoF) as a potential mitochondria-specific positron emission tomography radiotracer[J].J Labelled Comp Radiopharm, 2013, 56(14):717-721.DOI:10.1002/jlcr.3109.
[11] Zhao K, Zhao GM, Wu D, et al.Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury[J].J Biol Chem, 2004, 279(33): 34682-34690.DOI:10.1074/jbc.M402999200.
[12] Birk AV, Chao WM, Bracken C, et al.Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis[J].Br J Pharmacol, 2014, 171(8):2017-2028.DOI:10.1111/bph.12468.
[13] Wipf P, Xiao J, Jiang J, et al.Mitochondrial targeting of selective electron scavengers:synthesis and biological analysis of hemigramicidin-TEMPO conjugates[J].J Am Chem Soc, 2005, 127(36):12460-12461.DOI:10.1021/ja053679l.
[14] Hoye AT, Davoren JE, Wipf P, et al.Targeting mitochondria[J].Acc Chem Res, 2008, 41(1):87-97.DOI:10.1021/ar700135m.
[15] Xun Z, Rivera-Sánchez S, Ayala-Peáa S, et al.Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington’s disease[J].Cell Rep, 2012, 2(5):1137-1142.DOI:10.1016/j.celrep.2012.10.001.
[16] Gruber J, Fong S, Chen CB, et al.Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing[J].Biotechnol Adv, 2013, 31(5):563-592.DOI:10.1016/j.biotechadv.2012.09.005.
[17] Yamada Y, Akita H, Kogure K, et al.Mitochondrial drug delivery and mitochondrial disease therapy—an approach to liposome-based delivery targeted to mitochondria[J].Mitochondrion, 2007, 7(1/2):63-71.DOI:10.1016/j.mito.2006.12.003.
[18] Dolezal P, Likic V, Tachezy J, et al.Evolution of the molecular machines for protein import into mitochondria[J].Science, 2006, 313(5785):314-318.DOI:10.1126/science.1127895.
[19] Bohnert M, Pfanner N, van der Laan M.A dynamic machinery for import of mitochondrial precursor proteins[J].FEBS Lett, 2007, 581(15):2802-2810.DOI:10.1016/j.febslet.2007.03.004.
[20] Murcha MW, Kmiec B, Kubiszewski-Jakubiak S, et al.Protein import into plant mitochondria:signals, machinery, processing, and regulation[J].J Exp Bot, 2014, 65(22):6301-6335.DOI:10.1093/jxb/eru399.
[21] Bacman SR, Williams SL, Duan D, et al.Manipulation of mtDNA heteroplasmy in all striated muscles of newborn mice by AAV9-mediated delivery of a mitochondria-targeted restriction endonuclease[J].Gene Ther, 2012, 19(11):1101-1106.DOI:10.1038/gt.2011.196.
[22] Bacman SR, Williams SL, Hernandez D, et al.Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a ’differential multiple cleavage-site’ model[J].Gene Ther, 2007, 14(18):1309-1318.DOI:10.1038/sj.gt.3302981.
[23] Srivastava S, Moraes CT.Manipulating mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease[J].Hum Mol Genet, 2001, 10(26):3093-3099.DOI:10.1093/hmg/10.26.3093
[24] Tanaka M, Borgeld HJ, Zhang J, et al.Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria[J].J Biomed Sci, 2002, 9(6 Pt 1):534-541.DOI:10.1007/BF02254980.
[25] Esaki M, Kanamori T, Si N, et al.Two distinct mechanisms drive protein translocation across the mitochondrial outer membrane in the late step of the cytochrome b(2)import pathway[J].Proc Natl Acad Sci USA, 1999, 96(21):11770-11775.
[26] Kulawiak B, Höpker J, Gebert M, et al.The mitochondrial protein import machinery has multiple connections to the respiratory chain[J].Biochim Biophys Acta, 2013, 1827(5):612-626.DOI:10.1016/j.bbabio.2012.12.004.
[27] Torchilin VP, Rammohan R, Weissig V, et al.TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors[J].Proc Natl Acad Sci USA, 2001, 98(15): 8786-8791.DOI:10.1073/pnas.151247498.
[28] Joliot A, Prochiantz A.Transduction peptides:from technology to physiology[J].Nat Cell Biol, 2004, 6(3):189-196.DOI:10.1038/ncb0304-189.
[29] Torchilin VP, Rammohan R, Weissig V, et al.TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors[J].Proc Natl Acad Sci USA, 2001, 98(15):8786-8791.DOI:10.1073/pnas.151247498.
[30] Del GV, Mackenzie JA, Payne RM.Targeting proteins to mitochondria using TAT[J].Mol Genet Metab, 2003, 80(1/2):170-180.DOI:10.1016/j.ymgme.2003.08.017
[31] Shokolenko IN, Alexeyev MF, LeDoux SP, et al.TAT-mediated protein transduction and targeted delivery of fusion proteins into mitochondria of breast cancer cells[J].DNA Repair(Amst), 2005, 4(4):511-518.DOI:10.1016/j.dnarep.2004.11.009.
[32] Marin SE, Mesterman R, Robinson B, et al.Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations In NDUFV1 and NDUFS2[J].Gene, 2013, 516(1):162-167.DOI:10.1016/j.gene.2012.12.024.
[33] Mileshina D, Ibrahim N, Boesch P, et al.Mitochondrial transfection for studying organellar DNA repair, genome maintenance and aging[J].Mech Ageing Dev, 2011, 132(8/9):412-423.DOI:10.1016/j.mad.2011.05.002.
[34] D’Souza GG, Rammohan R, Cheng SM, et al.DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells[J].J Control Release, 2003, 92(1/2):189-197.DOI:10.1016/S0168-3659(03)00297-9.
[35] Kogure K, Moriguchi R, Sasaki K, et al.Development of a non-viral multifunctional envelope-type nano device by a novel lipid film hydration method[J].J Control Release, 2004, 98(2):317-323.DOI:10.1016/j.jconrel.2004.04.024.
[36] Kajimoto K, Sato Y, Nakamura T, et al.Multifunctional envelope-type nano device for controlled intracellular trafficking and selective targeting in vivo[J].J Control Release, 2014, 190:593-606.DOI:10.1016/j.jconrel.2014.03.058.
[37] Wang XX, Li YB, Yao HJ, et al.The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells[J].Biomaterials, 2011, 32(24):5673-5687.DOI:10.1016/j.biomaterials.2011.04.029.
[38] Biswas S, Dodwadkar NS, Deshpande PP, et al.Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo[J].J Control Release, 2012, 159(3):393-402.DOI:10.1016/j.jconrel.2012.01.009.
[39] Yamada Y, Harashima H.Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases[J].Adv Drug Deliv Rev, 2008, 60(13/14):1439-1462.DOI:10.1016/j.addr.2008.04.016.

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备注/Memo

备注/Memo:
收稿日期:2016-1-13;改回日期:。
基金项目:国家自然科学基金(81273005);天津市应用基础与前沿技术研究重点项目(14JCZDJC36400);北京协和医学院青年基金(33320140124);中国医学科学院放射医学研究所探索基金(1555)
通讯作者:徐文清,Email:xuwenqing@irm-cams.ac.cn
更新日期/Last Update: 1900-01-01