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Aptamer-conjugated upconversion nanoprobes assisted by magnetic separation for effective isolation and sensitive detection of circulating tumor cells

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Abstract

Detection of circulating tumor cells (CTCs) plays an important role in cancer diagnosis and prognosis. In this study, aptamer-conjugated upconversion nanoparticles (UCNPs) are used for the first time as nanoprobes to recognize tumor cells, which are then enriched by attaching with magnetic nanoparticles (MNPs) and placing in the presence of a magnetic field. Owing to the autofluorescencefree nature of upconversion luminescence imaging, as well as the use of magnetic separation to further reduce background signals, our technique allows for highly sensitive detection and collection of small numbers of tumor cells spiked into healthy blood samples, and shows promise for CTC detection in medical diagnostics.

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References

  1. Ghossein, R. A.; Carusone, L.; Bhattacharya, S. Review: Polymerase chain reaction detection of micrometastases and circulating tumor cells: Application to melanoma, prostate, and thyroid carcinomas. Diagn. Mol. Pathol. 1999, 8, 165–175.

    Article  Google Scholar 

  2. Wittekind, C.; Neid, M. Cancer invasion and metastasis. Oncology 2005, 69 (Suppl. 1), 14–16.

    Article  Google Scholar 

  3. Alunni-Fabbroni, M.; Sandri, M. T. Circulating tumour cells in clinical practice: Methods of detection and possible characterization. Methods 2010, 50, 289–297.

    Article  Google Scholar 

  4. Allard, W. J.; Matera, J.; Miller, M. C.; Repollet, M.; Connelly, M. C.; Rao, C.; Tibbe, A. G. J.; Uhr, J. W.; Terstappen, L. W. M. M. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin. Cancer Res. 2004, 10, 6897–6904.

    Article  Google Scholar 

  5. Maltez-da Costa, M.; de la Escosura-Muñiz, A.; Nogués, C.; Barrios, L.; Ibáñez, E.; Merkoci, A. Simple monitoring of cancer cells using nanoparticles. Nano Lett. 2012, 12, 4164–4171.

    Article  Google Scholar 

  6. Galanzha, E. I.; Shashkov, E. V.; Kelly, T.; Kim, J. W.; Yang, L.; Zharov, V. P. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat. Nanotechnol. 2009, 4, 855–860.

    Article  Google Scholar 

  7. Gazouli, M.; Lyberopoulou, A.; Pericleous, P.; Rizos, S.; Aravantinos, G.; Nikiteas, N.; Anagnou, N. P.; Efstathopoulos, E. P. Development of a quantum-dot-labelled magnetic immunoassay method for circulating colorectal cancer cell detection. World J. Gastroenterol. 2012, 18, 4419–4426.

    Article  Google Scholar 

  8. Zieglschmid, V.; Hollmann, C.; Böcher, O. Detection of disseminated tumor cells in peripheral blood. Crit. Rev. Clin. Lab. Sci. 2005, 42, 155–196.

    Article  Google Scholar 

  9. Park, G. S.; Kwon, H.; Kwak, D. W.; Park, S. Y.; Kim, M.; Lee, J. H.; Han, H.; Heo, S.; Li, X. S.; Lee, J. H. et al. Full surface embedding of gold clusters on silicon nanowires for efficient capture and photothermal therapy of circulating tumor cells. Nano Lett. 2012, 12, 1638–1642.

    Article  Google Scholar 

  10. Zhao, L. B.; Lu, Y. T.; Li, F. Q.; Wu, K.; Hou, S.; Yu, J. H.; Shen, Q. L.; Wu, D. X.; Song, M.; Ouyang, W. H. et al. High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing. Adv. Mater. 2013, 25, 2897–2902.

    Article  Google Scholar 

  11. Chen, L.; Liu, X. L.; Su, B.; Li, J.; Jiang, L.; Han, D.; Wang, S. T. Aptamer-mediated efficient capture and release of T lymphocytes on nanostructured surfaces. Adv. Mater. 2011, 23, 4376–4380.

    Article  Google Scholar 

  12. Wang, S. T.; Liu, K.; Liu, J.; Yu, Z. T. F.; Xu, X. W.; Zhao, L. B.; Lee, T.; Lee, E. K.; Reiss, J.; Lee, Y. K. et al. Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew. Chem. Int. Ed. 2011, 50, 3084–3088.

    Article  Google Scholar 

  13. Wu, L.; Wang, J. S.; Ren, J. S.; Qu, X. G. Ultrasensitive telomerase activity detection in circulating tumor cells based on DNA metallization and sharp solid-state electrochemical techniques. Adv. Funct. Mater. 2014, 24, 2727–2733.

    Article  Google Scholar 

  14. Chang, Y. S.; di Tomaso, E.; McDonald, D. M.; Jones, R.; Jain, R. K.; Munn, L. L. Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood. Proc. Natl. Acad. Sci. USA 2000, 97, 14608–14613.

    Article  Google Scholar 

  15. Auzel, F. Upconversion and anti-stokes processes with f and d ions in solids. Chem. Rev. 2004, 104, 139–174.

    Article  Google Scholar 

  16. Deng, M. L.; Ma, Y. X.; Huang, S.; Hu, G. F.; Wang, L. Y. Monodisperse upconversion NaYF4 nanocrystals: Syntheses and bioapplications. Nano Res. 2011, 4, 685–694.

    Article  Google Scholar 

  17. Idris, N. M.; Gnanasammandhan, M. K.; Zhang, J.; Ho, P. C.; Mahendran, R.; Zhang, Y. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat. Med. 2012, 18, 1580–1585.

    Article  Google Scholar 

  18. Wang, C.; Cheng, L.; Liu, Z. Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials. 2011, 32, 1110–1120.

    Article  Google Scholar 

  19. Cheng, L.; Yang, K.; Zhang, S.; Shao, M. W.; Lee, S.; Liu, Z. Highly-sensitive multiplexed in vivo imaging using pegylated upconversion nanoparticles. Nano Res. 2010, 3, 722–732.

    Article  Google Scholar 

  20. Yang, Y. M.; Shao, Q.; Deng, R. R.; Wang, C.; Teng, X.; Cheng, K.; Cheng, Z.; Huang, L.; Liu, Z.; Liu, X. G. In vitro and in vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. Angew. Chem. Int. Ed. 2012, 51, 3125–3129.

    Article  Google Scholar 

  21. Zhou, L.; Li, Z. H.; Liu, Z.; Yin, M. L.; Ren, J. S.; Qu, X. G. One-step nucleotide-programmed growth of porous upconversion nanoparticles: Application to cell labeling and drug delivery. Nanoscale. 2014, 6, 1445–1452.

    Article  Google Scholar 

  22. Yang, Y. Upconversion nanophosphors for use in bioimaging, therapy, drug delivery and bioassays. Michromchim. Acta 2014, 181, 263–294.

    Article  Google Scholar 

  23. Chen, F.; Bu, W. B.; Cai, W. B.; Shi, J. L. Engineering upconversion nanoparticles for biomedical imaging and therapy. In Engineering in Translational Medicine. Cai, W., Eds.; Springer: London, 2014; pp. 585–609.

    Chapter  Google Scholar 

  24. Xiong, L. Q.; Chen, Z. G.; Tian, Q. W.; Cao, T. Y.; Xu, C. J.; Li, F. Y. High contrast upconversion luminescence targeted imaging in vivo using peptide-labeled nanophosphors. Anal. Chem. 2009, 81, 8687–8694.

    Article  Google Scholar 

  25. He, L.; Feng, L. Z.; Cheng, L.; Liu, Y. M.; Li, Z. W.; Peng, R.; Li, Y. G.; Guo, L.; Liu, Z. Multilayer dual-polymer-coated upconversion nanoparticles for multimodal imaging and serum-enhanced gene delivery. ACS Appl. Mater. Interface 2013, 5, 10381–10388.

    Article  Google Scholar 

  26. Zvyagin, A. V.; Song, Z.; Nadort, A.; Sreenivasan, V. K. A.; Deyev, S. M. Luminescent nanomaterials for molecular-specific cellular imaging. In Handbook of Nano-Optics and Nanophotonics. Ohtsu, M., Eds.; Springer: Berlin Heidelberg, 2013; pp. 563–596.

    Chapter  Google Scholar 

  27. Wang, C.; Cheng, L.; Xu, H.; Liu, Z. Towards whole-body imaging at the single cell level using ultra-sensitive stem cell labeling with oligo-arginine modified upconversion nanoparticles. Biomaterials. 2012, 33, 4872–4881.

    Article  Google Scholar 

  28. Cheng, L.; Wang, C.; Ma, X. X.; Wang, Q. L.; Cheng, Y.; Wang, H.; Li, Y. G.; Liu, Z. Multifunctional upconversion nanoparticles for dual-modal imaging-guided stem cell therapy under remote magnetic control. Adv. Funct. Mater. 2013, 23, 272–280.

    Article  Google Scholar 

  29. Liu, C. H.; Wang, H.; Li, X.; Chen, D. P. Monodisperse, size-tunable and highly efficient β-NaYF4:Yb, Er (Tm) up-conversion luminescent nanospheres: Controllable synthesis and their surface modifications. J. Mater. Chem. 2009, 19, 3546–3553.

    Article  Google Scholar 

  30. Prencipe, G.; Tabakman, S. M.; Welsher, K.; Liu, Z.; Goodwin, A. P.; Zhang, L.; Henry, J.; Dai, H. PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. J. Am. Chem. Soc. 2009, 131, 4783–4787.

    Article  Google Scholar 

  31. Wang, C.; Ma, X. X.; Ye, S. Q.; Cheng, L.; Yang, K.; Guo, L.; Li, C. H.; Li, Y. G.; Liu, Z. Protamine functionalized single-walled carbon nanotubes for stem cell labeling and in vivo Raman/magnetic resonance/photoacoustic triple-modal imaging. Adv. Funct. Mater. 2012, 22, 2363–2375.

    Article  Google Scholar 

  32. Sun, S. H.; Zeng, H.; Robinson, D. B.; Raoux, S.; Rice, P. M.; Wang, S. X.; Li, G. X. Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. J. Am. Chem. Soc. 2004, 126, 273–279.

    Article  Google Scholar 

  33. Lee, H.; Yoon, T. J.; Figueiredo, J. L.; Swirski, F. K.; Weissleder, R. Rapid detection and profiling of cancer cells in fine-needle aspirates. Proc. Natl. Acad. Sci. USA 2009, 106, 12459–12464.

    Article  Google Scholar 

  34. Smith, J. E.; Medley, C. D.; Tang, Z. W.; Shangguan, D.; Lofton, C.; Tan, W. H. Aptamer-conjugated nanoparticles for the collection and detection of multiple cancer cells. Anal. Chem. 2007, 79, 3075–3082.

    Article  Google Scholar 

  35. Herr, J. K.; Smith, J. E.; Medley, C. D.; Shangguan, D.; Tan, W. H. Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells. Anal. Chem. 2006, 78, 2918–2924.

    Article  Google Scholar 

  36. Shangguan, D.; Cao, Z. H.; Meng, L.; Mallikaratchy, P.; Sefah, K.; Wang, H.; Li, Y.; Tan, W. H. Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J. Proteome Res. 2008, 7, 2133–2139.

    Article  Google Scholar 

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Authors and Affiliations

  1. Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, 215123, China

    Shuai Fang, Chao Wang, Jian Xiang, Liang Cheng, Xuejiao Song, Ligeng Xu, Rui Peng & Zhuang Liu

Authors
  1. Shuai Fang
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  2. Chao Wang
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  3. Jian Xiang
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  4. Liang Cheng
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  5. Xuejiao Song
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  6. Ligeng Xu
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  7. Rui Peng
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  8. Zhuang Liu
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Corresponding authors

Correspondence to Rui Peng or Zhuang Liu.

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These two authors contributed equally to this work.

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Fang, S., Wang, C., Xiang, J. et al. Aptamer-conjugated upconversion nanoprobes assisted by magnetic separation for effective isolation and sensitive detection of circulating tumor cells. Nano Res. 7, 1327–1336 (2014). https://doi.org/10.1007/s12274-014-0497-9

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  • DOI: https://doi.org/10.1007/s12274-014-0497-9

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