基于亲脂性阳离子、线粒体靶向信号肽和己糖激酶修饰的线粒体靶向抗肿瘤制剂的研究进展
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摘要
目的:为研发更优的用于肿瘤治疗的线粒体靶向制剂提供参考。方法:以"线粒体靶向""抗肿瘤""亲脂性阳离子""线粒体靶向信号肽""己糖激酶""Mitochondrial targeting""Antitumor""Lipophilic cation""Mitochondrial targeting signal peptide""Hexokinase"等为关键词,组合查询2002年1月-2018年7月在中国知网、万方数据、维普网、PubMed、Elsevier、SpringerLink等数据库中发表的相关文献,从亲脂性阳离子、线粒体靶向信号肽和己糖激酶等3个方面,对线粒体靶向抗肿瘤制剂进行论述。结果与结论:共检索到相关文献132篇,其中有效文献38篇。对药物表面进行修饰,可以获得主动靶向线粒体的抗肿瘤制剂。现有的靶向修饰载体有亲脂性阳离子、线粒体靶向信号肽和己糖激酶等。其中,亲脂性阳离子主要分为三苯基膦(TPP)和地喹氯铵囊泡状聚合体(DQAsomes),TPP可凭借其特殊的化学结构穿过脂质双分子层,DQAsomes具备穿透脂质双分子层然后聚集到线粒体的特性。线粒体靶向信号肽利用其转运功能实现线粒体靶向。己糖激酶与线粒体的结合体能促进肿瘤细胞生长,因此阻碍己糖激酶与线粒体的结合可以作为肿瘤治疗的另一研究热点。未来研究方向,应利用靶向肿瘤细胞线粒体这一特性,寻找或开发出更优的用于肿瘤治疗的线粒体靶向制剂,以进一步提高肿瘤的治疗效果。
引文
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[22]CHENG SM,PABBA S,TORCHILIN VP,et al.Towards mitochondria-specific delivery of apoptosis-inducing agents:DQAsomal incorporated paclitaxel[J].J Drug Del Sci Tech,2005,15(1):81-86.
[23]LI N,ZHANG CX,Wang XX,et al.Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways[J].Biomaterials,2013,34(13):3366-3380.
[24]陈航,牛秀然,高嫒嫒,等.线粒体信号肽引导葡萄糖调节蛋白75-增强型绿色荧光蛋白(GRP75-EGFP)融合蛋白定位于线粒体[J].细胞与分子免疫学杂志,2016,32(10):1311-1316.
[25]JORES T,KLINGER A,GRO?LE,et al.Characterization of the targeting signal in mitochondrialβ-barrel proteins[J].Nat Commun,2016.DOI:10.1038/ncomms12036.
[26]ZHANG C,LIU Z,BUNKER E,et al.Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response[J].J Biol Chem,2017,292(36):15105-15120.
[27]YAMADA Y,HARASHIMA H.Enhancement in selective mitochondrial association by direct modification of a mitochondrial targeting signal peptide on a liposomal based nanocarrier[J].Mitochondrion,2012,13(5):526-532.
[28]何晓晓,袁媛,石慧,等.信号肽功能化二氧化硅纳米颗粒的线粒体靶向作用研究[J].高等学校化学学报,2009,30(12):2376-2380.
[29]MELIN J,KILISCH M,NEUMANN P,et al.A presequence-binding groove in Tom70 supports import of Mdl1into mitochondria[J].Biochim Biophys Acta,2015.DOI:10.1016/j.bbamcr.2015.04.021.
[30]袁媛.基于功能化纳米颗粒的线粒体识别及细胞荧光成像研究[D].长沙:湖南大学,2010.
[31]SHEARD MA,GHENT MV,CABRAL DJ,et al.Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration[J].Exp Cell Res,2015,334(1):78-89.
[32]GORLACH S,FICHNA J,LEWANDOWSKA U.Polyphenols as mitochondria-targeted anticancer drugs[J].Cancer Lett,2015,366(2):141-149.
[33]GOGVADZE V,ORRENIUS S,ZHIVOTOVSKY B.Mitochondria in cancer cells:what is so special about them?[J].Trends in Cell Biol,2018,18(4):165-173.
[34]SHOSHAN-BARMATZ V,BEN-HAIL D,ADMONI L,et al.The mitochondrial voltage-dependent anion channel1 in tumor cells[J].Biochim Biophys Acta,2015.DOI:10.1016/j.bbamem.2014.10.040.
[35]KIM W,YOON JH,JEONG JM,et al.Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma[J].Mol Cancer Ther,2007,6(9):2554-2562.
[36]ROBERTS DJ,TAN-SAH VP,DING EY,et al.Hexokinase-Ⅱpositively regulates glucose starvation-induced autophagy through TORC1 inhibition[J].Mol Cell,2014,53(4):521-533.
[37]YANG Y,GAO N,HU Y,et al.Gold nanoparticle-enhanced photodynamic therapy:effects of surface charge and mitochondrial targeting[J].Ther Deliv,2015,6(3):307-321.
[38]YE J,LI J,XIA R,et al.Prohibitin protects proximal tubule epithelial cells against oxidative injury through mitochondrial pathways[J].Free Radic Res,2015,49(11):1393-1403.
[2]宋再伟,谈志远,赵荣生.我国肿瘤临床治疗现行指南制定的现状分析及循证指南评价[J].中国药房,2018,29(13):1729-1734.
[3]MIAO L,GUO S,LIN CM,et al.Nanoformulations for combination or cascade anticancer therapy[J].Adv Drug Deliv Rev,2017.DOI:10.1016/j.addr.2017.06.003.
[4]JAHANBAN-ESFAHLAN R,SEIDI K,BANIMOHAM-AD-SHOTORBANI B,et al.Combination of nanotechnology with vascular targeting agents for effective cancer therapy[J].J Cell Physiol,2018,233(4):2982-2992.
[5]PRANATHARTHIHARAN S,PATEL MD,MALSHE VC,et al.Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma[J].Drug Deliv,2017,24(1):20-29.
[6]PRAKASH A,DOUBLIéS.Base excision repair in the mitochondria[J].J Cell Biochem,2015,116(8):1490-1499.
[7]WANG Y,GUO SH,SHANG XJ,et al.Triptolide induces Sertoli cell apoptosis in mice via ROS/JNK-dependent activation of the mitochondrial pathway and inhibition of Nrf2-mediated antioxidant response[J].Acta Pharmacol Sin,2018,39(2):311-327.
[8]ZOROVA LD,POPKOV VA,PLOTNIKOV EY,et al.Mitochondrial membrane potential[J].Anal Biochem,2017.DOI:10.1016/j.ab.2017.07.009.
[9]UNCHWANIWALA N,SHERER NM,LOEB DD.Hepatitis B virus polymerase localizes to the mitochondria,and its terminal protein domain contains the mitochondrial targeting signal[J].J Virol,2016,90(19):8705-8719.
[10]KRASNOV GS,DMITRIEV AA,LAKUNINA VA,et al.Targeting VDAC-bound hexokinaseⅡ:a promising approach for concomitant anti-cancer therapy[J].Expert Opin Ther Targets,2013,17(10):1221-1233.
[11]刘爱赟,侯晓双,丁娅.基于线粒体靶向机制的抗肿瘤制剂的研究进展[J].药学学报,2017,52(6):879-887.
[12]SAFIN DA,MITORAJ MP,ROBEYNS K,et al.Luminescent mononuclear mixed ligand complexes of copper(I)with 5-phenyl-2,2′-bipyridine and triphenylphosphine[J].Dalton Trans,2015,44(38):16824-16832.
[13]LEE Y,THOMPSON DH.Stimuli-responsive liposomes for drug delivery[J].WIREs Nanomed Nanobiotechnol,2017.DOI:10.1002/wnan.1450.
[14]KRISHNAMURTHY S,VAIYAPURI R,ZHANG L,et al.Lipid-coated polymeric nanoparticles for cancer drug delivery[J].Biomater Sci,2015,3(7):923-936.
[15]SHIN DH,KWON GS.Epothilone B-based 3-in-1 polymeric micelle for anticancer drug therapy[J].Int J Pharm,2017,518(1/2):307-311.
[16]NGWULUKA NC,KOTAK DJ,DEVARAJAN PV.Design and characterization of metformin-loaded solid lipid nanoparticles for colon cancer[J].AAPS PharmSciTech,2017,18(2):358-368.
[17]BODDAPATI SV,D’SOUZA GGM,ERDOGAN S,et al.Organelle-targeted nanocarriers:specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo[J].Nano Lett,2008,8(8):2559-2563.
[18]STOVER TC,SHARMA A,ROBERTSON GP,et al.Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma[J].Clin Cancer Res,2005,11(9):3465-3474.
[19]段佳,程丽芳,丁伯美,等.RGD修饰的线粒体靶向长循环脂质体的制备及初步体外评价[J].中国医药工业杂志,2017,48(4):516-521.
[20]LEE JH,KIM KY,JIN HY,et al.Self-assembled coumarin nanoparticle in aqueous solution as selective mitochondrial-targeting drug delivery system[J].ACS Appl Mater Interfaces,2018,10(4):3380-3391.
[21]PATHAK RK,KOLISHETTI N,DHAR S.Targeted nanoparticles in mitochondrial medicine[J].WIREs Nanomed Nanobiotechnol,2015,7(3):315-329.
[22]CHENG SM,PABBA S,TORCHILIN VP,et al.Towards mitochondria-specific delivery of apoptosis-inducing agents:DQAsomal incorporated paclitaxel[J].J Drug Del Sci Tech,2005,15(1):81-86.
[23]LI N,ZHANG CX,Wang XX,et al.Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways[J].Biomaterials,2013,34(13):3366-3380.
[24]陈航,牛秀然,高嫒嫒,等.线粒体信号肽引导葡萄糖调节蛋白75-增强型绿色荧光蛋白(GRP75-EGFP)融合蛋白定位于线粒体[J].细胞与分子免疫学杂志,2016,32(10):1311-1316.
[25]JORES T,KLINGER A,GRO?LE,et al.Characterization of the targeting signal in mitochondrialβ-barrel proteins[J].Nat Commun,2016.DOI:10.1038/ncomms12036.
[26]ZHANG C,LIU Z,BUNKER E,et al.Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response[J].J Biol Chem,2017,292(36):15105-15120.
[27]YAMADA Y,HARASHIMA H.Enhancement in selective mitochondrial association by direct modification of a mitochondrial targeting signal peptide on a liposomal based nanocarrier[J].Mitochondrion,2012,13(5):526-532.
[28]何晓晓,袁媛,石慧,等.信号肽功能化二氧化硅纳米颗粒的线粒体靶向作用研究[J].高等学校化学学报,2009,30(12):2376-2380.
[29]MELIN J,KILISCH M,NEUMANN P,et al.A presequence-binding groove in Tom70 supports import of Mdl1into mitochondria[J].Biochim Biophys Acta,2015.DOI:10.1016/j.bbamcr.2015.04.021.
[30]袁媛.基于功能化纳米颗粒的线粒体识别及细胞荧光成像研究[D].长沙:湖南大学,2010.
[31]SHEARD MA,GHENT MV,CABRAL DJ,et al.Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration[J].Exp Cell Res,2015,334(1):78-89.
[32]GORLACH S,FICHNA J,LEWANDOWSKA U.Polyphenols as mitochondria-targeted anticancer drugs[J].Cancer Lett,2015,366(2):141-149.
[33]GOGVADZE V,ORRENIUS S,ZHIVOTOVSKY B.Mitochondria in cancer cells:what is so special about them?[J].Trends in Cell Biol,2018,18(4):165-173.
[34]SHOSHAN-BARMATZ V,BEN-HAIL D,ADMONI L,et al.The mitochondrial voltage-dependent anion channel1 in tumor cells[J].Biochim Biophys Acta,2015.DOI:10.1016/j.bbamem.2014.10.040.
[35]KIM W,YOON JH,JEONG JM,et al.Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma[J].Mol Cancer Ther,2007,6(9):2554-2562.
[36]ROBERTS DJ,TAN-SAH VP,DING EY,et al.Hexokinase-Ⅱpositively regulates glucose starvation-induced autophagy through TORC1 inhibition[J].Mol Cell,2014,53(4):521-533.
[37]YANG Y,GAO N,HU Y,et al.Gold nanoparticle-enhanced photodynamic therapy:effects of surface charge and mitochondrial targeting[J].Ther Deliv,2015,6(3):307-321.
[38]YE J,LI J,XIA R,et al.Prohibitin protects proximal tubule epithelial cells against oxidative injury through mitochondrial pathways[J].Free Radic Res,2015,49(11):1393-1403.