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. 2010 Oct 7;1(9):842–846. doi: 10.1007/s13238-010-0110-2

Aptamer-based and DNAzyme-linked colorimetric detection of cancer cells

Xiaoli Zhu 1, Ya Cao 2, Zhiqiang Liang 1, Genxi Li 1,2,✉
PMCID: PMC4875232  PMID: 21203926

Abstract

This paper reports a novel method to detect human leukemic lymphoblasts (CCRF-CEM cells). While the aptamer of the cancer cells was employed as the recognition element to target cancer cells, peroxidaseactive DNAzyme was used as the sensing element to produce catalysis-induced colorimetric signals. The elegant architecture integrating the aptamer and DNAzyme made it feasible to detect cancer cells easily and rapidly by the color change of the substrate for DNAzyme. Experimental results showed that 500 cells can well indicate the cancer, while as control, 250,000 Islet Island Beta cells only show tiny signals, suggesting that the method proposed in this paper has considerable sensitivity and selectivity. Furthermore, since it does not require expensive apparatus, or modification or label of DNA chains, the method we present here is also cost-effective and conveniently operated, implying potential applications in future cancer diagnosis.

Keywords: CCRF-CEM acute leukemia cells, aptamer, DNAzyme, colorimetry

References

  1. Baker B.R., Lai R.Y., Wood M.S., Doctor E.H., Heeger A.J., Plaxco K.W. An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids. J Am Chem Soc. 2006;128:3138–3139. doi: 10.1021/ja056957p. [DOI] [PubMed] [Google Scholar]
  2. Chen X., Estévez M.C., Zhu Z., Huang Y.F., Chen Y., Wang L., Tan W. Using aptamer-conjugated fluorescence resonance energy transfer nanoparticles for multiplexed cancer cell monitoring. Anal Chem. 2009;81:7009–7014. doi: 10.1021/ac9011073. [DOI] [PubMed] [Google Scholar]
  3. Degefa T.H., Kwak J. Label-free aptasensor for platelet-derived growth factor (PDGF) protein. Anal Chim Acta. 2008;613:163–168. doi: 10.1016/j.aca.2008.03.010. [DOI] [PubMed] [Google Scholar]
  4. Ellington A.D., Szostak J.W. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990;346:818–822. doi: 10.1038/346818a0. [DOI] [PubMed] [Google Scholar]
  5. Espina V., Geho D., Mehta A.I., Petricoin E.F., Liotta L.A., Rosenblatt K.P. Pathology of the future: molecular profiling for targeted therapy. Cancer Invest. 2005;23:36–46. doi: 10.1081/CNV-46434. [DOI] [PubMed] [Google Scholar]
  6. Famulok M., Mayer G., Blind M. Nucleic acid aptamers-from selection in vitro to applications in vivo. Acc Chem Res. 2000;33:591–599. doi: 10.1021/ar960167q. [DOI] [PubMed] [Google Scholar]
  7. Ghossein R.A., Bhattacharya S. Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours. Eur J Cancer. 2000;36:1681–1694. doi: 10.1016/S0959-8049(00)00152-0. [DOI] [PubMed] [Google Scholar]
  8. He F., Shen Q., Jiang H., Zhou J., Cheng J., Guo D., Li Q., Wang X., Fu D., Chen B. Rapid identification and high sensitive detection of cancer cells on the gold nanoparticle interface by combined contact angle and electrochemical measurements. Talanta. 2009;77:1009–1014. doi: 10.1016/j.talanta.2008.07.063. [DOI] [PubMed] [Google Scholar]
  9. Herr J.K., Smith J.E., Medley C.D., Shangguan D., Tan W. Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells. Anal Chem. 2006;78:2918–2924. doi: 10.1021/ac052015r. [DOI] [PubMed] [Google Scholar]
  10. Kroemer G., Pouyssegur J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell. 2008;13:472–482. doi: 10.1016/j.ccr.2008.05.005. [DOI] [PubMed] [Google Scholar]
  11. Liu C.W., Huang C.C., Chang H.T. Highly selective DNA-based sensor for lead(II) and mercury(II) ions. Anal Chem. 2009;81:2383–2387. doi: 10.1021/ac8022185. [DOI] [PubMed] [Google Scholar]
  12. Luo J., Isaacs W.B., Trent J.M., Duggan D.J. Looking beyond morphology: cancer gene expression profiling using DNA microarrays. Cancer Invest. 2003;21:937–949. doi: 10.1081/CNV-120025096. [DOI] [PubMed] [Google Scholar]
  13. Medley C.D., Smith J.E., Tang Z., Wu Y., Bamrungsap S., Tan W. Gold nanoparticle-based colorimetric assay for the direct detection of cancerous cells. Anal Chem. 2008;80:1067–1072. doi: 10.1021/ac702037y. [DOI] [PubMed] [Google Scholar]
  14. Osborne S.E., Ellington A.D. Nucleic acid selection and the challenge of combinatorial chemistry. Chem Rev. 1997;97:349–370. doi: 10.1021/cr960009c. [DOI] [PubMed] [Google Scholar]
  15. Padgett J.K., Parlette H.L., English J.C. A diagnosis of chronic lymphocytic leukemia prompted by cutaneous lymphocytic infiltrates present in mohs micrographic surgery frozen sections. Dermatol Surg. 2003;29:769–771. doi: 10.1046/j.1524-4725.2003.29194.x. [DOI] [PubMed] [Google Scholar]
  16. Pan C., Guo M., Nie Z., Xiao X., Yao S. Aptamer-based electrochemical sensor for label-free recognition and detection of cancer cells. Electroanalysis. 2009;21:1321–1326. doi: 10.1002/elan.200804563. [DOI] [Google Scholar]
  17. Paredes-Aguilera R., Romero-Guzman L., Lopez-Santiago N., Burbano-Ceron L., Camacho-Del Monte O., Nieto-Martinez S. Flow cytometric analysis of cell-surface and intracellular antigens in the diagnosis of acute leukemia. Am J Hematol. 2001;68:69–74. doi: 10.1002/ajh.1155. [DOI] [PubMed] [Google Scholar]
  18. Pui C.H., Evans W.E. Acute lymphoblastic leukemia. N Engl J Med. 1998;339:605–615. doi: 10.1056/NEJM199808273390907. [DOI] [PubMed] [Google Scholar]
  19. Shangguan D., Li Y., Tang Z., Cao Z.C., Chen H.W., Mallikaratchy P., Sefah K., Yang C.J., Tan W. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci U S A. 2006;103:11838–11843. doi: 10.1073/pnas.0602615103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shao N., Wickstrom E., Panchapakesan B. Nanotubeantibody biosensor arrays for the detection of circulating breast cancer cells. Nanotechnology. 2008;19:465101. doi: 10.1088/0957-4484/19/46/465101. [DOI] [PubMed] [Google Scholar]
  21. Smith J.E., Medley C.D., Tang Z., Shangguan D., Lofton C., Tan W. Aptamer-conjugated nanoparticles for the collection and detection of multiple cancer cells. Anal Chem. 2007;79:3075–3082. doi: 10.1021/ac062151b. [DOI] [PubMed] [Google Scholar]
  22. Tuerk C., Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249:505–510. doi: 10.1126/science.2200121. [DOI] [PubMed] [Google Scholar]
  23. Weerkamp F., Dekking E., Ng Y.Y., van der Velden V.H.J., Wai H., Böttcher S., Brüggemann M., van der Sluijs A.J., Koning A., Boeckx N., et al. Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in leukemia patients. Leukemia. 2009;23:1106–1117. doi: 10.1038/leu.2009.93. [DOI] [PubMed] [Google Scholar]
  24. Xiao Y., Piorek B.D., Plaxco K.W., Heeger A.J. A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement. J Am Chem Soc. 2005;127:17990–17991. doi: 10.1021/ja056555h. [DOI] [PubMed] [Google Scholar]

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