Skip to main content

Advertisement

SpringerLink
Log in

MUC1 Aptamer-Based Near-Infrared Fluorescence Probes for Tumor Imaging

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

DNA aptamer (APT) is able to bind to Mucin 1 (MUC1) specifically. The possibility of APT acting as a moiety to construct tumor-targeting probes was investigated.

Procedures

A near-infrared (NIR) fluorescent dye (MPA) and polyethylene glycol (PEG) were conjugated to APT to form APT-MPA and APT-PEG-MPA. The successful synthesis of the two probes was characterized via thin layer chromatography (TLC) and optical spectra. The tumor-targeting efficacy of the probes was evaluated in detail at cell level and animal level, respectively.

Results

The results indicated that MPA and PEG were successfully coupled with APT. APT-based probes were mediated by Mucin 1 into tumor cells, and PEG-modified probe exhibited higher cell affinity.

Conclusions

The aptamer-based NIR fluorescent probes are promising candidates for tumor imaging and diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

References

  1. Mukhopadhyay P, Chakraborty S, Ponnusamy MP et al (2011) Mucins in the pathogenesis of breast cancer: implications in diagnosis, prognosis and therapy. Biochim Biophys Acta 1815:224–240

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Dasanu CA, Sethi N, Ahmed N (2012) Immune alterations and emerging immunotherapeutic approaches in lung cancer. Expert Opin Biol Ther 12:923–937

    Article  CAS  PubMed  Google Scholar 

  3. Bafna S, Kaur S, Batra SK (2010) Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene 29:2893–2904

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Pillai K, Pourgholami MH, Chua TC, Morris DL (2013) MUC1 as a potential target in anticancer therapies. Am J Clin Oncol. doi:10.1097/COC. 0b013e31828f5a07

    PubMed  Google Scholar 

  5. Cao Y, Karsten U (2001) Binding patterns of 51 monoclonal antibodies to peptide and carbohydrate epitopes of the epithelial mucin (MUC1) on tissue sections of adenolymphomas of the parotid (Warthin’s tumours): role of epitope masking by glycans. Histochem Cell Biol 115:349–356

    CAS  PubMed  Google Scholar 

  6. Salouti M, Babaei HM, Rajabi H (2011) Comparison of (99 m)Tc- labeled PR81 and its F(ab')2 fragments as radioimmunoscintigraphy agents for breast cancer imaging. Ann Nucl Med 25:87–92

    Article  CAS  PubMed  Google Scholar 

  7. Seuma J, Bunch J, Cox A et al (2008) Combination of immunohistochemistry and laser ablation ICP mass spectrometry for imaging of cancer biomarkers. Proteomics 8:3775–3784

    Article  CAS  PubMed  Google Scholar 

  8. Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10:282–289

    Article  CAS  PubMed  Google Scholar 

  9. Bouchard PR, Hutabarat RM, Thompson KM (2010) Discovery and development of therapeutic aptamers. Annu Rev Pharmacol Toxicol 50:237–257

    Article  CAS  PubMed  Google Scholar 

  10. Germer K, Leonard M, Zhang X (2013) RNA aptamers and their therapeutic and diagnostic applications. Int J Biochem Mol Biol 4:27–40

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Hu M, Zhang K (2013) The application of aptamers in cancer research: an up-to-date review. Future Oncol 9:369–376

    Article  CAS  PubMed  Google Scholar 

  12. Kim JK, Choi KJ, Lee M et al (2012) Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle. Biomaterials 33:207–217

    Article  CAS  PubMed  Google Scholar 

  13. Savla R, Taratula O, Garbuzenko O et al (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release 153:16–22

    Article  CAS  PubMed  Google Scholar 

  14. Ghoroghchian PP, Therien MJ, Hammer DA (2009) In vivo fluorescence imaging: a personal perspective. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:156–167

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Luo S, Zhang E, Su Y et al (2011) A review of NIR dyes in cancer targeting and imaging. Biomaterials 32:7127–7138

    Article  CAS  PubMed  Google Scholar 

  16. Shan L, Xue J, Guo J et al (2011) Improved targeting of ligand-modified adenovirus as a new near infrared fluorescence tumor imaging probe. Bioconjug Chem 22:567–581

    Article  CAS  PubMed  Google Scholar 

  17. Guo J, Du C, Shan L (2012) Comparison of near-infrared fluorescent deoxyglucose probes with different dyes for tumor diagnosis in vivo. Contrast Media Mol Imaging 7:289–301

    Article  CAS  PubMed  Google Scholar 

  18. Chen H, Li B, Wang C et al (2013) Characterization of a fluorescence probe based on gold nanoclusters for cell and animal imaging. Nanotechnology 24:055704–055713

    Article  PubMed  Google Scholar 

  19. Liu F, Deng D, Chen F et al (2010) Folate-polyethylene glycol conjugated near-infrared fluorescence probe with high targeting affinity and sensitivity for in vivo early tumor diagnosis. Mol Imaging Biol 12:595–607

    Article  PubMed  Google Scholar 

  20. Mahounga DM, Shan L, Jie C (2012) Synthesis of a novel L-methyl-methionine-MPA fluorescent probe for in vivo near infrared imaging of tumors. Mol Imaging Biol 14:699–707

    Article  PubMed  Google Scholar 

  21. Ferreira CS, Matthews CS, Missailidis S et al (2006) DNA aptamers that bind to MUC1 tumour marker: design and characterization of MUC1-binding single-stranded DNA aptamers. Tumour Biol 27:289–301

    Article  CAS  PubMed  Google Scholar 

  22. Devine PL, Birrell GW, Whitehead RH et al (1992) Expression of MUC1 and MUC2 mucins by human tumor cell lines. Tumor Biology 13:268–277

    Article  CAS  PubMed  Google Scholar 

  23. Croce MV, Colussi AG, Price MR et al (1999) Identification and characterization of different subpopulations in a human lung adenocarcinoma cell line (A549). Pathol Oncol Res 5:197–204

    Article  CAS  PubMed  Google Scholar 

  24. Gursahani H, Riggs-Sauthier J, Pfeiffer J et al (2009) Absorption of polyethylene glycol (PEG) polymers: the effect of PEG size on permeability. J Pharm Sci 98:2847–2856

    Article  CAS  PubMed  Google Scholar 

  25. Trujillo CA, Nery AA, Alves JM et al (2007) Development of the anti-VEGF aptamer to a therapeutic agent for clinical ophthalmology. Clin Ophthalmol 1:393–402

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Hicke BJ, Stephens AW, Gould T et al (2006) Tumor targeting by an aptamer. J Nucl Med 47:668–678

    CAS  PubMed  Google Scholar 

  27. Ko HY, Choi KJ, Lee CH, Kim S (2011) A multimodal nanoparticle-based cancer imaging probe simultaneously targeting nucleolin, integrin αvβ3 and tenascin-C proteins. Biomaterials 32:1130–1138

    Article  CAS  PubMed  Google Scholar 

  28. Kim D, Jeong YY, Jon S (2010) A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano 4:3689–3696

    Article  CAS  PubMed  Google Scholar 

  29. Wang T, Ray J (2012) Aptamer-based molecular imaging. Protein Cell 3:739–754

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Natural Science Foundation Committee of China (NSFC 61335007, 81371684, 81220108012, 81000666, 81171395, and 81328012), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (no. SKLNMZZYQ201403), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions for their financial support.

Conflict of Interest

The authors declare that they have no conflicts of interest

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing, 210009, China

    Haiyan Chen, Juan Zhao, Min Zhang, Yuxiang Ma & Yueqing Gu

  2. School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing, 210009, China

    Haibo Yang

Authors
  1. Haiyan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haibo Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuxiang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yueqing Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yueqing Gu.

Additional information

Haiyan Chen, Juan Zhao, and Min Zhang contributed equally to this work.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 90 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, H., Zhao, J., Zhang, M. et al. MUC1 Aptamer-Based Near-Infrared Fluorescence Probes for Tumor Imaging. Mol Imaging Biol 17, 38–48 (2015). https://doi.org/10.1007/s11307-014-0763-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-014-0763-y

Key words

Search

Navigation