title: Oligonucleotide aptamers: new tools for targeted cancer therapy.
abstract: Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed "chemical antibodies." In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Jilin, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Sirnaomics Inc., Gaithersburg, Maryland, USA.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Lu
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Roberto R
authors.initials: RR
authors.lastname: Rosato
authors.affiliation: School of Biosciences and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
references.citation: Chem Commun (Camb). 2006 Aug 14;(30):3229-31
references.pmid: 17028752
references.citation: Biochem Biophys Res Commun. 2012 Mar 2;419(1):60-5
references.pmid: 22326915
references.citation: Annu Rev Med. 2005;56:555-83
references.pmid: 15660527
references.citation: Chem Asian J. 2013 Oct;8(10):2417-22
references.pmid: 23757285
references.citation: Retina. 2002 Apr;22(2):143-52
references.pmid: 11927845
references.citation: Curr Opin Mol Ther. 2008 Apr;10(2):116-23
references.pmid: 18386223
references.citation: J Pharm Sci. 2012 May;101(5):1672-7
references.pmid: 22383033
references.citation: Macromol Biosci. 2011 Oct 10;11(10):1331-5
references.pmid: 21818856
references.citation: Cancer Sci. 2011 May;102(5):991-8
references.pmid: 21281402
references.citation: Nucleic Acids Res. 2006 Jun 01;34(10):e73
references.pmid: 16740739
references.citation: Small. 2013 Oct 25;9(20):3477-84
references.pmid: 23609964
references.citation: Anal Chem. 2007 Jul 1;79(13):4900-7
references.pmid: 17530817
references.citation: Bioconjug Chem. 2012 Nov 21;23(11):2192-200
references.pmid: 23043415
references.citation: Nucleic Acid Ther. 2011 Jun;21(3):173-8
references.pmid: 21749294
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11838-43
references.pmid: 16873550
references.citation: J Proteome Res. 2008 May;7(5):2133-9
references.pmid: 18363322
references.citation: PLoS One. 2011;6(6):e20299
references.pmid: 21687663
references.citation: Sci Transl Med. 2011 Jan 19;3(66):66ra6
references.pmid: 21248316
references.citation: J Biol Chem. 2001 Dec 28;276(52):48644-54
references.pmid: 11590140
references.citation: Anal Chem. 2004 Jul 15;76(14):4066-75
references.pmid: 15253644
references.citation: Nat Commun. 2014 Mar 12;5:3459
references.pmid: 24619206
references.citation: Anal Chem. 2010 Oct 15;82(20):8642-9
references.pmid: 20873781
references.citation: Eur J Pharm Sci. 2013 Oct 9;50(2):191-7
references.pmid: 23835028
references.citation: Target Oncol. 2012 Dec;7(4):217-25
references.pmid: 23179556
references.citation: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8170-5
references.pmid: 23630281
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6315-20
references.pmid: 16606824
references.citation: Anal Chem. 2013 Apr 16;85(8):4141-9
references.pmid: 23480100
references.citation: Angew Chem Int Ed Engl. 2006 Dec 11;45(48):8149-52
references.pmid: 17099918
references.citation: Nature. 2004 Nov 11;432(7014):173-8
references.pmid: 15538359
references.citation: Nucleic Acid Ther. 2013 Dec;23(6):435-42
references.pmid: 24152208
references.citation: Mol Ther. 2012 Dec;20(12):2291-303
references.pmid: 22910292
references.citation: Chembiochem. 2009 Mar 23;10(5):862-8
references.pmid: 19253922
references.citation: Biochemistry. 2012 Oct 23;51(42):8321-3
references.pmid: 23057694
references.citation: Biotechnol Appl Biochem. 2011 Jul-Aug;58(4):226-30
references.pmid: 21838796
references.citation: Nucleic Acids Res. 2009 Feb;37(3):866-76
references.pmid: 19103663
references.citation: Biomaterials. 2013 Jul;34(21):5244-53
references.pmid: 23582862
references.citation: Sensors (Basel). 2012;12(1):612-31
references.pmid: 22368488
references.citation: Int J Cancer. 2013 Jun 1;132(11):2578-88
references.pmid: 23150432
references.citation: PLoS One. 2011;6(9):e24071
references.pmid: 21915281
references.citation: Proc Natl Acad Sci U S A. 2013 May 14;110(20):7998-8003
references.pmid: 23630258
references.citation: Anal Bioanal Chem. 2012 Jan;402(1):187-94
references.pmid: 22052153
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18460-5
references.pmid: 24167271
references.citation: Mol Ther Nucleic Acids. 2013 Jan 08;2:e67
references.pmid: 23299833
references.citation: J Nanobiotechnology. 2011 Jan 31;9:2
references.pmid: 21281497
references.citation: Clin Chem. 2009 Apr;55(4):813-22
references.pmid: 19246617
references.citation: J Am Chem Soc. 2009 Aug 12;131(31):11174-8
references.pmid: 19603808
references.citation: Nucleic Acids Res. 2009 May;37(9):3094-109
references.pmid: 19304999
references.citation: Oligonucleotides. 2010 Dec;20(6):317-23
references.pmid: 21133818
references.citation: PLoS One. 2010 Dec 10;5(12):e14269
references.pmid: 21170319
references.citation: Gastroenterology. 2012 Jul;143(1):155-65.e8
references.pmid: 22465431
references.citation: Biochem Biophys Res Commun. 2005 Dec 16;338(2):956-63
references.pmid: 16256939
references.citation: J Biomed Mater Res A. 2009 Sep 15;90(4):1152-61
references.pmid: 18671260
references.citation: Arch Med Res. 2011 Feb;42(2):88-96
references.pmid: 21565620
references.citation: Science. 1990 Aug 3;249(4968):505-10
references.pmid: 2200121
references.citation: Cancer Res. 2013 Mar 15;73(6):1934-45
references.pmid: 23467613
references.citation: Analyst. 2009 Sep;134(9):1808-14
references.pmid: 19684903
references.citation: Anal Bioanal Chem. 2007 Jan;387(1):171-82
references.pmid: 17072603
references.citation: Angew Chem Int Ed Engl. 2013 Jan 28;52(5):1472-6
references.pmid: 23233389
references.citation: Mol Ther Nucleic Acids. 2013 Jul 16;2:e107
references.pmid: 23860551
references.citation: Biomaterials. 2011 Mar;32(8):2124-32
references.pmid: 21147500
references.citation: PLoS One. 2010 Dec 07;5(12):e15004
references.pmid: 21165148
references.citation: Methods Mol Biol. 2014;1103:241-65
references.pmid: 24318899
references.citation: Cancer Res. 2012 Mar 15;72(6):1373-83
references.pmid: 22282665
references.citation: Mol Cancer Ther. 2006 Dec;5(12):2957-62
references.pmid: 17172400
references.citation: Biochemistry. 2010 Oct 26;49(42):9106-12
references.pmid: 20843027
references.citation: Leukemia. 2009 Feb;23(2):235-44
references.pmid: 19151784
references.citation: Nucleic Acids Res. 2003 May 15;31(10):e54
references.pmid: 12736320
references.citation: ACS Nano. 2010 Mar 23;4(3):1433-42
references.pmid: 20166743
references.citation: Biosens Bioelectron. 1999 May 31;14(5):457-64
references.pmid: 10451913
references.citation: Front Genet. 2012 Nov 02;3:234
references.pmid: 23130020
references.citation: J Photochem Photobiol B. 2013 Apr 5;121:67-74
references.pmid: 23524248
references.citation: Nucleic Acids Res. 2004 Nov 23;32(20):6120-8
references.pmid: 15562003
references.citation: Biotechnol Bioeng. 2012 Nov;109(11):2920-31
references.pmid: 22615073
references.citation: Nucleic Acids Res. 2012 Jul;40(13):6319-37
references.pmid: 22467215
references.citation: J Drug Target. 2013 Sep;21(8):739-44
references.pmid: 23815443
references.citation: Gene Ther. 2007 Feb;14(4):283-91
references.pmid: 17279100
references.citation: PLoS One. 2012;7(9):e43836
references.pmid: 22962591
references.citation: Nature. 1990 Aug 30;346(6287):818-22
references.pmid: 1697402
references.citation: J Inorg Biochem. 2013 Nov;128:124-30
references.pmid: 23954482
references.citation: Nat Protoc. 2010 Jun;5(6):1169-85
references.pmid: 20539292
references.citation: J Transl Med. 2012 Jul 20;10:148
references.pmid: 22817844
references.citation: Nat Protoc. 2010 Dec;5(12):1993-2004
references.pmid: 21127492
references.citation: Chem Commun (Camb). 2012 Oct 14;48(80):10043-5
references.pmid: 22936337
references.citation: Biomaterials. 2013 Dec;34(37):9728-35
references.pmid: 24044994
references.citation: Virology. 2013 Nov;446(1-2):325-33
references.pmid: 24074596
references.citation: PLoS One. 2012;7(2):e31970
references.pmid: 22384115
references.citation: Mol Ther. 2014 Apr;22(4):828-41
references.pmid: 24566984
references.citation: PLoS One. 2011;6(10):e26332
references.pmid: 22022604
references.citation: Eur J Pharm Sci. 2013 Jan 23;48(1-2):259-71
references.pmid: 23142634
references.citation: Chem Asian J. 2013 Oct;8(10):2370-6
references.pmid: 23907978
references.citation: Mol Immunol. 2014 Feb;57(2):236-46
references.pmid: 24200843
references.citation: PLoS One. 2010 Sep 30;5(9):
references.pmid: 20927342
references.citation: Biomaterials. 2013 May;34(15):3816-27
references.pmid: 23465488
references.citation: Biomaterials. 2013 Nov;34(35):8909-17
references.pmid: 23968853
references.citation: J Biol Chem. 2011 Jun 17;286(24):21896-905
references.pmid: 21531729
references.citation: J Pathol. 2009 Jul;218(3):327-36
references.pmid: 19291713
references.citation: PLoS One. 2013;8(3):e57341
references.pmid: 23483901
references.citation: Nucleic Acid Ther. 2013 Dec;23(6):401-7
references.pmid: 24171482
references.citation: PLoS One. 2010 Nov 01;5(11):e13770
references.pmid: 21072169
references.citation: Chem Asian J. 2012 Jun;7(7):1630-6
references.pmid: 22492537
references.citation: Adv Mater. 2011 Sep 22;23(36):H278-82
references.pmid: 21833996
references.citation: PLoS One. 2012;7(5):e37789
references.pmid: 22662223
references.citation: PLoS One. 2012;7(10):e42731
references.pmid: 23056171
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17356-61
references.pmid: 18978032
references.citation: ACS Chem Neurosci. 2011 Jan 31;2(3):175-181
references.pmid: 21892384
references.citation: Biomaterials. 2011 Nov;32(31):8010-20
references.pmid: 21788069
references.citation: J Mater Chem B. 2013 Oct 21;1(39):5288-5297
references.pmid: 24159374
references.citation: Oncotarget. 2011 Apr;2(4):298-304
references.pmid: 21666286
references.citation: Curr Cancer Drug Targets. 2008 Nov;8(7):554-65
references.pmid: 18991566
references.citation: Gynecol Oncol. 2013 Nov;131(2):451-9
references.pmid: 23933187
references.citation: Mol Ther Nucleic Acids. 2013 Jun 11;2:e98
references.pmid: 23756353
references.citation: Arch Immunol Ther Exp (Warsz). 2013 Aug;61(4):255-71
references.pmid: 23563807
references.citation: Biomaterials. 2010 Jun;31(16):4592-9
references.pmid: 20206379
references.citation: Mol Ther. 2008 Aug;16(8):1481-9
references.pmid: 18461053
references.citation: Mol Cell Proteomics. 2007 Dec;6(12):2230-8
references.pmid: 17875608
references.citation: Nucleic Acids Res. 2002 Dec 1;30(23):e132
references.pmid: 12466564
references.citation: Nucleic Acids Res. 2013 Apr;41(7):4266-83
references.pmid: 23470998
references.citation: Nat Biotechnol. 2006 Aug;24(8):1005-15
references.pmid: 16823371
references.citation: Small. 2013 Nov 11;9(21):3678-84
references.pmid: 23661612
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1850-5
references.pmid: 21233423
references.citation: Ophthalmology. 2003 May;110(5):979-86
references.pmid: 12750101
references.citation: Cancer Res. 2002 Jul 15;62(14):4029-33
references.pmid: 12124337
references.citation: Cancer Lett. 2013 Mar 1;330(1):84-95
references.pmid: 23196060
references.citation: Mol Ther Nucleic Acids. 2012 May 15;1:e21
references.pmid: 23344001
references.citation: Nat Chem Biol. 2010 Jan;6(1):22-4
references.pmid: 19946274
references.citation: PLoS One. 2011;6(9):e24077
references.pmid: 21912664
references.citation: Nat Biotechnol. 2007 Oct;25(10):1119-26
references.pmid: 17921997
references.citation: Mol Vis. 2012;18:2783-95
references.pmid: 23213278
references.citation: ACS Nano. 2011 Oct 25;5(10):8131-9
references.pmid: 21936502
references.citation: Adv Drug Deliv Rev. 2011 Nov;63(14-15):1361-70
references.pmid: 22016112
references.citation: Nucleic Acid Ther. 2012 Oct;22(5):295-305
references.pmid: 23030589
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9226-31
references.pmid: 12874383
references.citation: Curr Opin Chem Biol. 2008 Aug;12(4):448-56
references.pmid: 18644461
references.citation: Cancer Res. 2004 Nov 1;64(21):7668-72
references.pmid: 15520166
references.citation: PLoS One. 2009 Nov 24;4(11):e7971
references.pmid: 19956692
references.citation: Chembiochem. 2003 Oct 6;4(10):979-83
references.pmid: 14523914
references.citation: ChemMedChem. 2012 Jan 2;7(1):79-84
references.pmid: 22170627
references.citation: Nucleic Acids Res. 2004 Oct 27;32(19):5757-65
references.pmid: 15509871
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):5-10
references.pmid: 20080797
references.citation: PLoS Biol. 2005 Apr;3(4):e123
references.pmid: 15769183
references.citation: Nucleic Acid Ther. 2012 Aug;22(4):275-82
references.pmid: 22861487
references.citation: Tumour Biol. 2006;27(6):289-301
references.pmid: 17033199
references.citation: ChemMedChem. 2008 Jun;3(6):991-1001
references.pmid: 18338423