核酸适体在儿童恶性肿瘤诊断与靶向治疗中的研究进展

张毅彬, 王彦鹏, 刘静

中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (5) : 421-427.

PDF(1881 KB)
PDF(1881 KB)
中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (5) : 421-427. DOI: 10.7499/j.issn.1008-8830.2018.05.016
综述

核酸适体在儿童恶性肿瘤诊断与靶向治疗中的研究进展

  • 张毅彬, 王彦鹏, 刘静
作者信息 +

Research advances in the role of aptamers in the diagnosis and targeted therapy of pediatric cancer

  • ZHANG Yi-Bin, WANG Yan-Peng, LIU Jing
Author information +
文章历史 +

摘要

核酸适体(aptamer)是运用指数富集的配体系统进化技术(SELEX)从体外人工合成的随机寡核苷酸序列库中经过多轮筛选后得到的单链DNA或RNA,它可以高亲和力与金属离子、小分子、糖类、脂质以及蛋白质等靶标特异性结合,具有制备方便、热稳定性好、低免疫原性等优点。核酸适体在分子成像、生物传感、疾病早期诊断及药物靶向治疗等生物医学领域中有很大的应用潜能。在儿童恶性肿瘤中,核酸适体技术具有实现肿瘤的早期诊断以及靶向治疗的应用前景,可避免传统化疗带来的儿童生长发育障碍以及远期的脏器功能不良等副作用。本文总结了与儿童恶性肿瘤相关的核酸适体筛选与应用的研究进展。

Abstract

Aptamers are single-stranded DNA or RNA which are isolated from synthesized random oligonucleotide library in vitro via systematic evolution of ligands by exponential enrichment (SELEX) and can bind to metal ions, small molecules, carbohydrates, lipids, proteins, and others targets with high affinity and specificity. Aptamers have the advantages of simple preparation, good thermal stability, and low immunogenicity and have great potential in the medical fields such as molecular imaging, biosensing, early diagnosis of diseases, and targeted therapy. Aptamer technology may be useful for early diagnosis and targeted therapy of pediatric cancer, and may avoid the side effects of conventional chemotherapy, such as growth and development disorders and long-term organ dysfunction. This article reviews the latest research advances in the selection and application of aptamers for pediatric cancer.

关键词

核酸适体 / 恶性肿瘤 / 诊断 / 靶向治疗 / 儿童

Key words

Aptamer / Cancer / Diagnosis / Targeted therapy / Child

引用本文

导出引用
张毅彬, 王彦鹏, 刘静. 核酸适体在儿童恶性肿瘤诊断与靶向治疗中的研究进展[J]. 中国当代儿科杂志. 2018, 20(5): 421-427 https://doi.org/10.7499/j.issn.1008-8830.2018.05.016
ZHANG Yi-Bin, WANG Yan-Peng, LIU Jing. Research advances in the role of aptamers in the diagnosis and targeted therapy of pediatric cancer[J]. Chinese Journal of Contemporary Pediatrics. 2018, 20(5): 421-427 https://doi.org/10.7499/j.issn.1008-8830.2018.05.016

参考文献

[23] Zhao N, Pei SN, Qi J, et al. Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia[J]. Biomaterials, 2015, 67:42-51.
[24] Zümrüt HE, Batool S, Van N, et al. Structural optimization of an aptamer generated from Ligand-Guided Selection (LIGS) resulted in high affinity variant toward mIgM expressed on Burkitt's lymphoma cell lines[J]. Biochim Biophys Acta, 2017, 1861(7):1825-1832.
[25] Parekh P, Kamble S, Zhao N, et al. Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer[J]. Biomaterials, 2013, 34(35):8909-8917.
[26] Soldevilla MM, Villanueva H, Bendandi M, et al. 2-fluoro-RNA oligonucleotide CD40 targeted aptamers for the control of B lymphoma and bone-marrow aplasia[J]. Biomaterials, 2015, 67:274-285.
[27] Hicke BJ, Marion C, Chang YF, et al. Tenascin-C aptamers are generated using tumor cells and purified protein[J]. J Biol Chem, 2001, 276(52):48644-48654.
[28] Kishida S, Mu P, Miyakawa S, et al. Midkine promotes neuroblastoma through Notch2 signaling[J]. Cancer Res, 2013, 73(4):1318-1327.
[29] Zhai G, Iskandar M, Barilla K, et al. Characterization of RNA aptamer binding by the Wilms' tumor suppressor protein WT1[J]. Biochemistry, 2001, 40(7):2032-2040.
[30] Nalini V, Deepa PR, Raguraman R, et al. Targeting HMGA2 in retinoblastoma cells in vitro using the aptamer strategy[J]. Ocul Oncol Pathol, 2016, 2(4):262-269.
[31] Camorani S, Esposito CL, Rienzo A, et al. Inhibition of receptor signaling and of glioblastoma-derived tumor growth by a novel PDGFRβ aptamer[J]. Mol Ther, 2014, 22(4):828-841.
[32] Sefah K, Shangguan D, Xiong X, et al. Development of DNA aptamers using Cell-SELEX[J]. Nat Protoc, 2010, 5(6):1169-1185.
[33] Shangguan D, Li Y, Tang Z, et al. Aptamers evolved from live cells as effective molecular probes for cancer study[J]. Proc Natl Acad Sci U S A, 2006, 103(32):11838-11843.
[34] Sefah K, Tang ZW, Shangguan DH, et al. Molecular recognition of acute myeloid leukemia using aptamers[J]. Leukemia, 2009, 23(2):235-244.
[35] Yang M, Jiang G, Li W, et al. Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery[J]. J Hematol Oncol, 2014, 7:5.
[36] Shangguan D, Cao ZC, Li Y, et al. Aptamers evolved from cultured cancer cells reveal molecular differences of cancer cells in patient samples[J]. Clin Chem, 2007, 53(6):1153-1155.
[37] Tang Z, Shangguan D, Wang K, et al. Selection of aptamers for molecular recognition and characterization of cancer cells[J]. Anal Chem, 2007, 79(13):4900-4907.
[38] Parekh P, Kamble S, Zhao N, et al. Biostable ssDNA aptamers specific for Hodgkin lymphoma[J]. Sensors (Basel), 2013, 13(11):14543-14557.
[39] Wu Q, Wu L, Wang Y, et al. Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging[J]. Biosens Bioelectron, 2016, 80:1-8.
[40] Tan Y, Shi YS, Wu XD, et al. DNA aptamers that target human glioblastoma multiforme cells overexpressing epidermal growth factor receptor variant Ⅲ in vitro[J]. Acta Pharmacol Sin, 2013, 34(12):1491-1498.
[41] Kim Y, Wu Q, Hamerlik P, et al. Aptamer identification of brain tumor-initiating cells[J]. Cancer Res, 2013, 73(15):4923-4936.
[42] Kang D, Wang J, Zhang W, et al. Selection of DNA aptamers against glioblastoma cells with high affinity and specificity[J]. PLoS One, 2012, 7(10):e42731.
[43] Wu X, Liang H, Tan Y, et al. Cell-SELEX aptamer for highly specific radionuclide molecular imaging of glioblastoma in vivo[J]. PLoS One, 2014, 9(6):e90752.
[44] Aptekar S, Arora M, Lawrence CL, et al. Selective targeting to glioma with nucleic acid aptamers[J]. PLoS One, 2015, 10(8):e0134957.
[45] Amero P, Esposito CL, Rienzo A, et al. Identification of an interfering ligand aptamer for EphB2/3 receptors[J]. Nucleic Acid Ther, 2016, 26(2):102-110.
[46] Wang H, Liang J, Ma Y, et al. Identification of a novel molecular probe for recognition of human osteosarcoma cell using the cellSELEX method[J]. Int J Clin Exp Med, 2015, 8(10):18151-18157.
[47] Liang C, Li F, Wang L, et al. Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma[J]. Biomaterials, 2017, 147:68-85.
[48] Li W, Wang K, Zhao M, et al. Development of aptamer oligonucleotides as anticoagulants and antithrombotics for cardiovascular diseases:current status[J]. Thromb Res, 2014, 134(4):769-773.
[49] Ozalp VC, Kavruk M, Dilek O, et al. Aptamers:molecular tools for medical diagnosis[J]. Curr Top Med Chem, 2015, 15(12):1125-1137.
[50] Bahreyni A, Yazdian-Robati R, Ramezani M, et al. Identification and imaging of leukemia cells using dual-aptamer-functionalized graphene oxide complex[J]. J Biomater Appl, 2017, 32(1):74-81.
[51] Tan J, Yang N, Hu Z, et al. Aptamer-functionalized fluorescent silica nanoparticles for highly sensitive detection of leukemia cells[J]. Nanoscale Res Lett, 2016, 11(1):298.
[52] Khoshfetrat SM, Mehrgardi MA. Amplified detection of leukemia cancer cells using an aptamer-conjugated gold-coated magnetic nanoparticles on a nitrogen-doped graphene modified electrode[J]. Bioelectrochemistry, 2017, 114:24-32.
[53] Xi D, Li Z, Liu L, et al. Ultrasensitive detection of cancer cells combining enzymatic signal amplification with an aerolysin nanopore[J]. Anal Chem, 2018, 90(1):1029-1034.
[54] Wu X, Chen J, Wu M, et al. Aptamers:active targeting ligands for cancer diagnosis and therapy[J]. Theranostics, 2015, 5(4):322-344.
[55] Ueki R, Sando S. A DNA aptamer to c-Met inhibits cancer cell migration[J]. Chem Commun (Camb), 2014, 50(86):13131-13134.
[56] Subramanian N, Srimany A, Kanwar JR, et al. Nucleolinaptamer therapy in retinoblastoma:molecular changes and mass spectrometry-based imaging[J]. Mol Ther Nucleic Acids, 2016, 5(8):e358.

基金

国家自然科学基金(81470362);中南大学研究生自主探索创新项目基金(2017zzts356;2017zzts355)。


PDF(1881 KB)

Accesses

Citation

Detail

段落导航
相关文章

/