• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

线粒体靶向聚合物TPP-PEI-LND的构建及其特性

张兵锋, 姜虎林

张兵锋, 姜虎林. 线粒体靶向聚合物TPP-PEI-LND的构建及其特性[J]. 中国药科大学学报, 2015, 46(6): 659-664. DOI: 10.11665/j.issn.1000-5048.20150604
引用本文: 张兵锋, 姜虎林. 线粒体靶向聚合物TPP-PEI-LND的构建及其特性[J]. 中国药科大学学报, 2015, 46(6): 659-664. DOI: 10.11665/j.issn.1000-5048.20150604
ZHANG Bingfeng, JIANG Hulin. Construction and characterization of mitochondria-targeted TPP-PEI-LND[J]. Journal of China Pharmaceutical University, 2015, 46(6): 659-664. DOI: 10.11665/j.issn.1000-5048.20150604
Citation: ZHANG Bingfeng, JIANG Hulin. Construction and characterization of mitochondria-targeted TPP-PEI-LND[J]. Journal of China Pharmaceutical University, 2015, 46(6): 659-664. DOI: 10.11665/j.issn.1000-5048.20150604

线粒体靶向聚合物TPP-PEI-LND的构建及其特性

基金项目: 江苏省自然科学基金资助项目(No.BK20140659)

Construction and characterization of mitochondria-targeted TPP-PEI-LND

  • 摘要: 以低相对分子质量聚乙烯亚胺(PEI)为骨架,将线粒体靶向基团三苯基膦(TPP)和化疗药物氯尼达明(LND)以酰胺键接枝到PEI上,构建线粒体靶向聚合物TPP-PEI-LND。TPP-PEI-LND经1H NMR确证。采用透析法考察TPP-PEI-LND的体外释放。采用HeLa细胞研究TPP-PEI-LND的线粒体靶向能力和细胞毒性。结果显示,TPP-PEI-LND线粒体靶向聚合物制备成功,其释药行为呈现缓释特点,并可以靶向递送药物到达线粒体,显著增强药物对肿瘤细胞的疗效。
    Abstract: The mitochondria-targeted TPP-PEI-LND was synthesized by mitochondria-targeted ligand triphenylphosphine(TPP)and therapeutic drug lonidamine(LND)conjugated to low molecular weight branched polyethyleneimine(PEI). TPP-PEI-LND was verified using 1H NMR; in vitro release was determined by the dialysis. Besides, the cytotoxicity and mitochondria-targeted potential of TPP-PEI-LND were investigated in HeLa cells. The results showed that TPP-PEI-LND was successfully synthesized and it exhibited the feature of extended-release. Hence, TPP-PEI-LND could deliver LND to mitochondria, resulting in significantly enhanced efficacy of LND.
  • [1] Fulda S,Galluzzi L,Kroemer G.Targeting mitochondria for cancer therapy[J].Nat Rev Drug Discov,2010,9(6):447-464.
    [2] Marrache S,Dhar S.Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics[J].Proc Natl Acad Sci U S A,2012,109(40):16288-16293.
    [3] Di Cosimo S,Ferretti G,Papaldo P,et al.Lonidamine:efficacy and safety in clinical trials for the treatment of solid tumors[J].Drugs Today(Barc),2003,39(3):157-174.
    [4] 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.
    [5] Ringsdorf H.Structure and properties of pharmacologically active polymers[C].J Polym Sci Symp,1975,51(1):135-153.
    [6] Hoste K,De Winne K,Schacht E.Polymeric prodrugs[J].Int J Pharm,2004,277(1):119-131.
    [7] Cuchelkar V,Kopecková P,Kopecek J.Novel HPMA copolymer-bound constructs for combined tumor and mitochondrial targeting[J].Mol Pharm,2008,5(5):776-786.
    [8] Wang M,Hu H,Sun Y,et al.A pH-sensitive gene delivery system based on folic acid-PEG-chitosan-PAMAM-plasmid DNA complexes for cancer cell targeting[J].Biomaterials,2013,34(38):10120-10132.
    [9] Roy K,Ghosn B,Kasturi SP.Enhancing polysaccharide-mediated delivery of nucleic acids through functionalization with secondary and tertiary amines[J].Curr Top Med Chem,2008,8(4):331-340.
    [10] Nel AE,Mödler L,Velegol D,et al.Understanding biophysicochemical interactions at the nano-bio interface[J].Nat Mater,2009,8(7):543-557.
    [11] Mo R,Sun Q,Xue J,et al.Multistage pH-responsive liposomes for mitochondrial-targeted anticancer drug delivery[J].Adv Mater,2012,24(27):3659-3665.
    [12] Duncan R,Vicent MJ.Polymer therapeutics-prospects for 21st century:the end of the beginning[J].Adv Drug Deliv Rev,2013,65(1):60-70.
    [13] Hu X,Hu J,Tian J,et al.Polyprodrug amphiphiles:hierarchical assemblies for shape-regulated cellular internalization,trafficking,and drug delivery[J].J Am Chem Soc,2013,135(46):17617-17629.
    [14] Jiang HL,Kim YK,Arote R,et al.Chitosan-graft-polyethylenimine as a gene carrier[J].J Control Release,2007,117(2):273-280.
    [15] Kunath K,von Harpe A,Fischer D,et al.Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery:comparison of physicochemical properties,transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine[J].J Control Release,2003,89(1):113-125.
    [16] Hu Q,Gao M,Feng G,et al.Mitochondria-targeted cancer therapy using a light-up probe with aggregation-induced-emission characteristics[J].Angew Chem Int Edit,2014,53(51):14225-14229.
    [17] Silvestrini B,Palazzo G,De Gregorio M.Lonidamine and related compounds[J].Prog Med Chem,1984,21:111-135.
    [18] Georg IG,Tash JS,Chakrasali R,et al.Lonidamine analogues and treatment of polycystic kidney disease:US,8362031[P].2013-01-29.
计量
  • 文章访问数:  1356
  • HTML全文浏览量:  3
  • PDF下载量:  2514
  • 被引次数: 0
出版历程
  • 刊出日期:  2015-12-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭