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Nucleic acid aptamers for clinical diagnosis: cell detection and molecular imaging

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Abstract

Nucleic acid aptamers have recently attracted significant attention in the field of clinical diagnosis because they have numerous merits, such as high affinity, high specificity, small size, little immunogenicity, stable structures, and ease of synthesis. This review focuses on discussing the potential applications of aptamers in cell detection and molecular imaging. For the ex vivo cell detection, this review discusses the status of five strategies: endogenous nucleic acid analysis, flow cytometry analysis, nanoparticle-based cell sensing, microfluidic cell separation, and histological examination. This review also discusses in vivo molecular and cell imaging by introducing aptamer-based molecular imaging, cell imaging, and integrated imaging and therapy. On the basis of the status of these promising studies, this review summarizes several challenging issues and unmet needs that may require more effort or attention in the future.

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References

  1. Boguski MS, McIntosh MW (2003) Nature 422:233–237

    Article  CAS  Google Scholar 

  2. Goding JW (ed) (1996) Monoclonal antibodies: principles and practice. Academic, San Diego

    Google Scholar 

  3. Gold L (1995) J Biol Chem 270:13581–13584

    CAS  Google Scholar 

  4. Ellington AD, Szostak JW (1990) Nature 346:818–822

    Article  CAS  Google Scholar 

  5. Jayasena SD (1999) Clin Chem 45:1628–1650

    CAS  Google Scholar 

  6. Lee JH, Yigit MV, Mazumdar D, Lu Y (2010) Adv Drug Deliv Rev 62:592–605

    Article  CAS  Google Scholar 

  7. Tombelli S, Minunni A, Mascini A (2005) Biosens Bioelectrons 20:2424–2434

    Article  CAS  Google Scholar 

  8. Lonnberg H (2009) Bioconjug Chem 20:1065–1094

    Article  CAS  Google Scholar 

  9. Remmele RL, Enk JZV, Dharmavaram V, Balaban D, Durst M, Shoshitaishvili A, Rand H (2005) J Am Chem Soc 127:8328–8339

    Article  CAS  Google Scholar 

  10. Gold L, Polisky B, Uhlenbeck O, Yarus M (1995) Annu Rev Biochem 64:763–797

    Article  CAS  Google Scholar 

  11. Burmeister PE, Lewis SD, Silva RF, Preiss JR, Horwitz LR, Pendergrast PS, McCauley TG, Kurz JC, Epstein DM, Wilson C, Keefe AD (2005) Chem Biol 12:25–33

    Article  CAS  Google Scholar 

  12. Fang X, Tan W (2010) Acc Chem Res 43:48–57

    Article  CAS  Google Scholar 

  13. Balamurugan S, Obubuafo A, Soper SA, Spivak DA (2008) Anal Bioanal Chem 390:1009–1021

    Article  CAS  Google Scholar 

  14. Gopinath SC (2007) Anal Bioanal Chem 387:171–182

    Article  CAS  Google Scholar 

  15. Mairal T, Ozalp VC, Lozano Sanchez P, Mir M, Katakis I, O'Sullivan CK (2008) Anal Bioanal Chem 390:989–1007

    Article  CAS  Google Scholar 

  16. Lee JO, So HM, Jeon EK, Chang H, Won K, Kim YH (2008) Anal Bioanal Chem 390:1023–1032

    Article  CAS  Google Scholar 

  17. Zhou J, Battig MR, Wang Y (2010) Anal Bioanal Chem 398:2471–2480

    Article  CAS  Google Scholar 

  18. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF (2004) N Engl J Med 351:781–791

    Article  CAS  Google Scholar 

  19. Diehn M, Cho RW, Clarke MF (2009) Semin Radiat Oncol 19:78–86

    Article  Google Scholar 

  20. Ring A, Smith IE, Dowsett M (2004) Lancet Oncol 5:79–88

    Article  Google Scholar 

  21. Hicke BJ, Watson SR, Koenig A, Lynott CK, Bargatze RF, Chang YF, Ringquist S, Moon-McDermott L, Jennings S, Fitzwater T, Han HL, Varki N, Albinana I, Willis MC, Varki A, Parma D (1996) J Clin Invest 98:2688–2692

    Article  CAS  Google Scholar 

  22. Zhou J, Soontornworajit B, Wang Y (2010) Biomacromolecules 11:2087–2093

    Article  CAS  Google Scholar 

  23. Smith JE, Medley CD, Tang Z, Shangguan D, Lofton C, Tan W (2007) Anal Chem 79:3075–3082

    Article  CAS  Google Scholar 

  24. Phillips JA, Xu Y, Xia Z, Fan ZH, Tan W (2009) Anal Chem 81:1033–1039

    Article  CAS  Google Scholar 

  25. Hicke BJ, Stephens AW, Gould T, Chang YF, Lynott CK, Heil J, Borkowski S, Hilger CS, Cook G, Warren S, Schmidt PG (2006) J Nucl Med 47:668–678

    CAS  Google Scholar 

  26. Shangguan DH, Meng L, Cao ZHC, Xiao ZY, Fang XH, Li Y, Cardona D, Witek RP, Liu C, Tan WH (2008) Anal Chem 80:721–728

    Article  CAS  Google Scholar 

  27. Proske D, Blank M, Buhmann R, Resch A (2005) Appl Microbiol Biotechnol 69:367–374

    Article  CAS  Google Scholar 

  28. Li SH, Xu H, Ding HM, Huang YP, Cao XX, Yang G, Li J, Xie ZG, Meng YH, Li XB, Zhao Q, Shen BF, Shao NS (2009) J Pathol 218:327–336

    Article  CAS  Google Scholar 

  29. Sozzi G, Conte D, Leon M, Ciricione R, Roz L, Ratcliffe C, Roz E, Cirenei N, Bellomi M, Pelosi G, Pierotti MA, Pastorino U (2003) J Clin Oncol 21:3902–3908

    Article  CAS  Google Scholar 

  30. Pallisgaard N, Clausen N, Schroder H, Hokland P (1999) Genes Chromosom Cancer 26:355–365

    Article  CAS  Google Scholar 

  31. Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ, Beaudry GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC, Hermeking H, Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello JM, Polyak K, Zawel L, Kinzler KW et al (1999) Nat Genet 23:387–388

    Article  CAS  Google Scholar 

  32. Berteau P, Dumas F, Gala JL, Eschwege P, Lacour B, Philippe M, Loric S (1998) Clin Chem 44:677–679

    CAS  Google Scholar 

  33. Goeminne JC, Guillaume T, Salmon M, Machiels JP, D'Hondt V, Symann M (1999) Bone Marrow Transplant 24:769–775

    Article  CAS  Google Scholar 

  34. Jung R, Kruger W, Hosch S, Holweg M, Kroger N, Gutensohn K, Wagener C, Neumaier M, Zander AR (1998) Br J Cancer 78:1194–1198

    Article  CAS  Google Scholar 

  35. Brossart P, Keilholz U, Scheibenbogen C, Mohler T, Willhauck M, Hunstein W (1994) J Immunother Emphasis Tumor Immunol 15:38–41

    CAS  Google Scholar 

  36. Brossart P, Schmier JW, Kruger S, Willhauck M, Scheibenbogen C, Mohler T, Keilholz U (1995) Cancer Res 55:4065–4068

    CAS  Google Scholar 

  37. Foss AJ, Guille MJ, Occleston NL, Hykin PG, Hungerford JL, Lightman S (1995) Br J Cancer 72:155–159

    Article  CAS  Google Scholar 

  38. Brown M, Wittwer C (2000) Clin Chem 46:1221–1229

    CAS  Google Scholar 

  39. Davis KA, Abrams B, Lin Y, Jayasena SD (1996) Nucleic Acids Res 24(4):702–706

    Article  CAS  Google Scholar 

  40. Ringquist S, Parma D (1998) Cytometry 33:394–405

    Article  CAS  Google Scholar 

  41. Mammen M, Choi SK, Whitesides GM (1998) Angew Chem Int Ed 37:2755–2794

    Article  CAS  Google Scholar 

  42. Kim Y, Cao Z, Tan W (2008) Proc Natl Acad Sci USA 105:5664–5669

    Article  CAS  Google Scholar 

  43. Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, Heller G (2009) Lancet Oncol 10:233–239

    Article  CAS  Google Scholar 

  44. Telford WG, King LE, Fraker PJ (1994) J Immunol Methods 172:1–16

    Article  CAS  Google Scholar 

  45. Tsavellas G, Huang A, McCullough T, Patel H, Araia R, Allen-Mersh TG (2002) Clin Exp Metastasis 19:495–502

    Article  CAS  Google Scholar 

  46. Agasti SS, Rana S, Park MH, Kim CK, You CC, Rotello VM (2010) Adv Drug Deliv Rev 62:316–328

    Article  CAS  Google Scholar 

  47. Medley CD, Smith JE, Tang Z, Wu Y, Bamrungsap S, Tan W (2008) Anal Chem 80(4):1067–1072

    Article  CAS  Google Scholar 

  48. Herr JK, Smith JE, Medley CD, Shangguan D, Tan W (2006) Anal Chem 78:2918–2924

    Article  CAS  Google Scholar 

  49. Elghanian R, Storhoff JJ, Mucic RC, Letsinger RL, Mirkin CA (1997) Science 277:1078–1081

    Article  CAS  Google Scholar 

  50. Oita I, Halewyck H, Thys B, Rombaut B, Vander Heyden Y, Mangelings D (2010) Anal Bioanal Chem 398:239–264

    Article  CAS  Google Scholar 

  51. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M (2007) Nature 450:1235–U1210

    Article  CAS  Google Scholar 

  52. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA (2008) N Engl J Med 359:366–377

    Article  CAS  Google Scholar 

  53. Henke C, Bitterman P, Roongta U, Ingbar D, Polunovsky V (1996) Am J Pathol 149:1639–1650

    CAS  Google Scholar 

  54. Mayumi M, Sumimoto S, Kanazashi S, Hata D, Yamaoka K, Higaki Y, Ishigami T, Kim KM, Heike T, Katamura K (1996) J Allergy Clin Immunol 98(6 Pt 2):S238–S247

    Article  CAS  Google Scholar 

  55. Plouffe BD, Brown MA, Iyer RK, Radisic M, Murthy SK (2009) Lab Chip 9:1507–1510

    Article  CAS  Google Scholar 

  56. Xu Y, Phillips JA, Yan JL, Li QG, Fan ZH, Tan WH (2009) Anal Chem 81:7436–7442

    Article  CAS  Google Scholar 

  57. Dharmasiri U, Balamurugan S, Adams AA, Okagbare PI, Obubuafo A, Soper SA (2009) Electrophoresis 30:3289–3300

    Article  CAS  Google Scholar 

  58. Wan Y, Kim Y-t, Li N, Cho SK, Bachoo R, Ellington AD, Iqbal SM (2010) Cancer Res 70:9371–9380

    Article  CAS  Google Scholar 

  59. Flores LM, Kindelberger DW, Ligon AH, Capelletti M, Fiorentino M, Loda M, Cibas ES, Janne PA, Krop IE (2010) Br J Cancer 102:1495–1502

    Article  CAS  Google Scholar 

  60. Wang ZP, Eisenberger MA, Carducci MA, Partin AW, Scher HI, Ts'o PO (2000) Cancer 88:2787–2795

    Article  CAS  Google Scholar 

  61. Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janicke F, Jackson S, Gornet T, Cristofanilli M, Pantel K (2007) Clin Cancer Res 13:920–928

    Article  CAS  Google Scholar 

  62. Zhang Z, Guo L, Guo A, Xu H, Tang J, Guo X, Xie J (2010) Bioorg Med Chem 18:8016–8025

    Article  CAS  Google Scholar 

  63. Zhang ZY, Guo L, Tang JJ, Guo XJ, Xie JW (2009) Talanta 80:985–990

    Article  CAS  Google Scholar 

  64. Dasilva JL, Lacombe C, Bruneval P, Casadevall N, Leporrier M, Camilleri JP, Bariety J, Tambourin P, Varet B (1990) Blood 75:577–582

    CAS  Google Scholar 

  65. Acs G, Zhang PJ, Rebbeck TR, Acs P, Verma A (2002) Cancer 95(5):969–981

    Article  CAS  Google Scholar 

  66. Thirstrup D, Baird GS (2010) Anal Chem 82:2498–2504

    Article  CAS  Google Scholar 

  67. Charlton J, Sennello J, Smith D (1997) Chem Biol 4:809–816

    Article  CAS  Google Scholar 

  68. Dougan H, Weitz JI, Stafford AR, Gillespie KD, Klement P, Hobbs JB, Lyster DM (2003) Nucl Med Biol 30:61–72

    Article  CAS  Google Scholar 

  69. Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ (1995) J Cell Biol 131:775–789

    Article  CAS  Google Scholar 

  70. Singh R, Bandyopadhyay D (2007) Cancer Biol Ther 6:481–486

    Article  CAS  Google Scholar 

  71. Pieve CD, Perkins AC, Missailidis S (2009) Nucl Med Biol 36:703–710

    Article  Google Scholar 

  72. Aslan K, Lakowicz JR, Geddes CD (2004) Anal Biochem 330:145–155

    Article  CAS  Google Scholar 

  73. Javier DJ, Nitin N, Levy M, Ellington A, Richards-Kortum R (2008) Bioconjug Chem 19:1309–1312

    Article  CAS  Google Scholar 

  74. Bagalkot V, Zhang L, Levy-Nissenbaum E, Jon S, Kantoff PW, Langer R, Farokhzad OC (2007) Nano Lett 7:3065–3070

    Article  CAS  Google Scholar 

  75. Wang AZ, Bagalkot V, Vasilliou CC, Gu F, Alexis F, Zhang L, Shaikh M, Yuet K, Cima MJ, Langer R, Kantoff PW, Bander NH, Jon S, Farokhzad OC (2008) Chem Med Chem 3:1311–1315

    CAS  Google Scholar 

  76. Kim D, Jeong YY, Jon S (2010) ACS Nano 4:3689–3696

    Article  CAS  Google Scholar 

  77. O'Connell D, Koenig A, Jennings S, Hicke B, Han HL, Fitzwater T, Chang YF, Varki N, Parma D, Varki A (1996) Proc Natl Acad Sci USA 93:5883–5887

    Article  Google Scholar 

  78. Causey LD, Dwyer DS (1996) Nat Biotechnol 14:348–351

    Article  CAS  Google Scholar 

  79. Galustian C, Childs RA, Yuen CT, Hasegawa A, Kiso M, Lubineau A, Shaw G, Feizi T (1997) Biochemistry 36:5260–5266

    Article  CAS  Google Scholar 

  80. Wang Y (2009) IEEE Eng Med Biol Mag 28:10–11

    Article  Google Scholar 

  81. Wang Y, Yuan F (2006) Ann Biomed Eng 34:114–127

    Article  CAS  Google Scholar 

  82. Jain RK (2001) Adv Drug Deliv Rev 46:149–168

    Article  CAS  Google Scholar 

  83. Tong R, Coyle VJ, Tang L, Barger AM, Fan TM, Cheng J (2010) Microsc Res Tech 73:901–909

    Article  CAS  Google Scholar 

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Acknowledgements

The authors greatly acknowledge financial support from the US National Science Foundation (CBET-1033212). B.S. is in part supported by the Royal Thai Government Scholarship.

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Correspondence to Yong Wang.

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Soontornworajit, B., Wang, Y. Nucleic acid aptamers for clinical diagnosis: cell detection and molecular imaging. Anal Bioanal Chem 399, 1591–1599 (2011). https://doi.org/10.1007/s00216-010-4559-x

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