适配子介导转运在肿瘤靶向治疗中的研究进展
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摘要
适配子是生物分子的单链寡核苷酸配体,通过指数富集的配体系统进化技术从人工合成的单链随机寡核苷酸文库中筛选获得。本文从连接方式、治疗靶点、疗效、优缺点多个方面对适配子介导转运在靶向肿瘤化疗、核酸治疗、光动力疗法和光热疗法中的研究进展进行概述。指出以适配体靶向肿瘤的递送系统在肿瘤相关靶向治疗中发展迅速,但仍面临许多挑战。筛选更多靶点的高亲和力适配子,改进适配子与其他治疗药物的结合模式,改善药物的药代动力学是目前工作的重点。
Aptamers are single-stranded oligonucleotide ligands of bioligical molecules and are selected by systematic evolution of ligands by exponential enrichment from a synthetic library of random single-stranded oligonucleotides.This paper summarized the connection modes,therapeutic targets,curative effects,advantages and disadvantages of aptamer-mediated delivery in targeted chemotherapy,nucleic acid therapy,photodynamic therapy and photothermal therapy.The delivery system targeting aptamers develops rapidly in tumor-related targeted therapies,but still faces many challenges.The screening of high-affinity aptamers with more targets,improvement of binding mode of aptamers with other drugs,and amelioration of drug pharmacokinetics are the focus of the present work.
Aptamers are single-stranded oligonucleotide ligands of bioligical molecules and are selected by systematic evolution of ligands by exponential enrichment from a synthetic library of random single-stranded oligonucleotides.This paper summarized the connection modes,therapeutic targets,curative effects,advantages and disadvantages of aptamer-mediated delivery in targeted chemotherapy,nucleic acid therapy,photodynamic therapy and photothermal therapy.The delivery system targeting aptamers develops rapidly in tumor-related targeted therapies,but still faces many challenges.The screening of high-affinity aptamers with more targets,improvement of binding mode of aptamers with other drugs,and amelioration of drug pharmacokinetics are the focus of the present work.
引文
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[33]Idris N M,Gnasammandhan M K,Zhang J,et al.In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers[J].Nat Med,2012,18(10):1580-1585.
[34]Shiao Y S,Chiu H H,Wu P H,et al.Aptamer-functionalized gold nanoparticles as photoresponsive nanoplatform for codrug delivery[J].ACS Appl Mater Inter,2014,6(24):21832-21841.
[35]Zhang D,Zheng A X,Li J,et al.Tumor microenvironment activable self-Assembled DNA hybrids for pH and redox dualresponsive chemotherapy/PDT treatment of hepatocellular carcinoma[J].Adv Sci,2017,4(4):1600460.
[36]Stephanopoulos N,Tong G J,Hsiao S C,et al.Dual-surface modified virus capsids for targeted delivery of photodynamic agents to cancer cells[J].ACS Nano,2010,4(10):6014-6020.
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[38]Zhang D,Zheng A X,Li J,et al.Smart Cu(Ⅱ)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release,photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma[J].Theranostics,2017,7(1):164-179.
[39]Chuang E Y,Lin C C,Chen K J,et al.A FRET-guided,NIRresponsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release[J].Biomaterials,2016,93(2016):48-59.
[2]Tuerk C,Gold L.Systematic evolution of ligands by exponential enrichment:RNA ligands to bacteriophage T4DNA polymerase[J].Science,1990,249(4968):505-510.
[3]Ellington A D,Szostak J W.In vitro selection of RNA molecules that bind specific ligands[J].Nature,1990,346(6287):818-822.
[4]Inoue M,Kadonosono K,Yamane A,et al.Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration[J].Jpn J Ophthalmol,2015,59(3):173-178.
[5]Ye W L,Du J B,Zhang B L,et al.Cellular uptake and antitumor activity of DOX-hyd-PEG-FA nanoparticles[J].PLoS ONE,2014,9(5):e97358
[6]Wong K E,Mora M C,Skinner M,et al.Evaluation of PolyMPCDox prodrugs in a human ovarian tumor model[J].Mol Pharm,2016,13(5):1679-1687.
[7]Zhu G Z,Meng L,Ye M,et al.Self-Assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells[J].Chem-Asian J,2012,7(7):1630-1636.
[8]Xiang D X,Shigdar S,Bean A G,et al.Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery[J].Theranostics,2017,7(17):4071-4086.
[9]Trinh T L,Zhu G Z,Xiao X L,et al.A synthetic aptamer-drug adduct for targeted liver cancer therapy[J].PLoS ONE,2015,10(11):e0136673.
[10]Dua P,Lee D K,Kim S,et al.ALPPL2aptamer-mediated targeted delivery of 5-Fluoro-2′-deoxyuridine to pancreatic cancer[J].Nucleic Acid Ther,2015,25(4):180-187.
[11]Jiao J,Zou Q,Zou M H,et al.Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy[J].Neoplasma,2016,63(4):569-575.
[12]Wagner A,Platzgummer M,Kreismayr G,et al.GMP production of liposomes-a new industrial a-pproach[J].J Liposome Res,2006,16(3):311-319.
[13]Moosavian S A,Abnous K,Badiee A,et al.Improvement in the drug delivery and anti-tumor efficacy of PEGylated liposomal doxorubicin by targeting RNA aptamers in mice bearing breast tumormodel[J].Colloid Surface B,2016,139:228-236.
[14]Liu Z B,Li J W,Li J,et al.Mannan-modified Ad5-PTEN treatment combined with docetaxel improves the therapeutic effect in H22tumor-bearing mice[J].Int J Nanomed,2012,7:5039-5049.
[15]Xiao S L,Liu Z B,Deng R L,et al.Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo[J].J Control Release,2017,258:130-145.
[16]Taghdisi S M,Danesh N M,Lavaee P,et al.Double targeting,controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles[J].Mater Sci Eng C Mater Biol Appl,2016,61:753-761.
[17]Savla R,Taratula O,Garbuzenko O,et al.Tumor targeted quantum dot-mucin 1aptamer-doxorubicin conjugate for imaging and treatment of cancer[J].J Control Release,2011,153(1):16-22.
[18]Taghavi S,Nia A H,Abnous K,et al.Polyethylenimine-functionalized carbon nanotubes tagged with AS1411aptamer for combination gene and drug delivery into human gastric cancer cells[J].Int J Pharm,2017,516(1-2):301-312.
[19]Koch A,Kogel K H.New wind in the sails:improving the agronomic value of crop plants through RNAi-mediatedgene silencing[J].Plant Biotechnol J,2014,12(7):821-831.
[20]McNamaraⅡJ O 2nd,Andrechek E R,Wang Y,et al.Cell typespecific delivery of siRNAs with aptamer-siRNA chimeras[J].Nat Biotechnol,2006,24(8):1005-1015.
[21]Jeong H,Lee S H,Hwang Y,et al.Multivalent aptamer-RNA conjugates for simple and efficient delivery of doxorubicin/siRNA into multidrug-resistant cells[J].Macromol Biosci,2017,17(4).doi:10.1002/mabi.201600343.
[22]Ni X H,Zhang Y G,Ribas J,et al.Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts[J].J Clin Invest,2011,121(6):2383-2390.
[23]Dai F R,Zhang Y,Zhu X,et al.Anticancer role of MUC1aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation[J].Target Oncol,2012,7(4):217-225.
[24]Esposito C L,Cerchia L,Catuogno S,et al.Multifunctional aptamer-miRNA conjugates for targeted cancer therapy[J].Mol Ther,2014,22(6):1151-1163.
[25]Catuogno S,Rienzo A,Vito A D,et al.Selective delivery of therapeutic single strand antimiRs by aptamer-based conjugates[J].J Control Release,2015,210:147-159.
[26]Esposito C L,Nuzzo S,Kumar S A,et al.A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells[J].J Control Release,2016,238:43-57.
[27]Portnoy V,Huang V,Place R F,et al,Small RNA and transcriptional upregulation[J].Wires RNA,2011,2(5):748-760.
[28]Yoon S,Huang K W,Reebye V,et al.Targeted delivery of C/EBPα-saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo[J].Mol Ther,2016,24(6):1106-1116.
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[30]Li C L,Jiang W C,Hu Q T,et al.Enhancing DPYSL3gene expression via a promoter-targeted small activating RNA approach suppresses cancer cell motility and metastasis[J].Oncotarget,2016,7(16):22893-22910.
[31]Chu T C,Lavery L A,Faulkner S,et al.Aptamer:toxin conjugates that specifically target prostate tumor cells[J].Cancer Res,2006,66(12):5989-5992.
[32]Chen C H,Dellamaggior K R,Ouellette C P,et al.Aptamerbased endocytosis of a lysosomal enzyme[J].P Natl Acad Sic USA,2008,105(41):15908-15913.
[33]Idris N M,Gnasammandhan M K,Zhang J,et al.In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers[J].Nat Med,2012,18(10):1580-1585.
[34]Shiao Y S,Chiu H H,Wu P H,et al.Aptamer-functionalized gold nanoparticles as photoresponsive nanoplatform for codrug delivery[J].ACS Appl Mater Inter,2014,6(24):21832-21841.
[35]Zhang D,Zheng A X,Li J,et al.Tumor microenvironment activable self-Assembled DNA hybrids for pH and redox dualresponsive chemotherapy/PDT treatment of hepatocellular carcinoma[J].Adv Sci,2017,4(4):1600460.
[36]Stephanopoulos N,Tong G J,Hsiao S C,et al.Dual-surface modified virus capsids for targeted delivery of photodynamic agents to cancer cells[J].ACS Nano,2010,4(10):6014-6020.
[37]Gao J W,Wu C L,Deng D,et al.Direct synthesis of water-soluble aptamer-Ag2Squantum dots at ambient temperature for specific Imaging and photothermal therapy of cancer[J].Adv Healthc Mater,2016,5(18):2437-2449.
[38]Zhang D,Zheng A X,Li J,et al.Smart Cu(Ⅱ)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release,photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma[J].Theranostics,2017,7(1):164-179.
[39]Chuang E Y,Lin C C,Chen K J,et al.A FRET-guided,NIRresponsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release[J].Biomaterials,2016,93(2016):48-59.