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Science China Chemistry

, Volume 61, Issue 2, pp 184–191 | Cite as

cNGR-based synergistic-targeted NIR fluorescent probe for tracing and bioimaging of pancreatic ductal adenocarcinoma

  • Yan Tang
  • Andong Shao
  • Jun Cao
  • Hui Li
  • Qiang Li
  • Meiying Zeng
  • Ming Liu
  • Yingsheng Cheng
  • Weihong Zhu
Articles

Abstract

Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimaging targets, both aminopeptidase N (APN, known as CD13) and Caveolin-1 are found as upregulation on the cell membrane surface of PDAC, in which APN is the principal receptor of the cyclic peptide cNGR (Asn-Gly-Arg, NGR) and Caveolin-1 can synergistically mediate endocytosis in this receptor-targeted process. Herein, we conjugate cNGR to dicyanomethylene-4H-pyran (DCM) chromophore to develop a synergistic-targeted near-infrared (NIR) fluorescent probe DCM-cNGR with strongly intrinsic NIR fluorescence, stable optical performance, low cytotoxicity, and rapid accumulation in PANC-1 cells with the synergistic overexpressed APN receptor-targeted and Caveolin-1-mediated endocytosis. As demonstrated, DCM-cNGR can realize noninvasive NIR imaging for targeting PANC-1 tumor in vivo after intravenous injection into PANC-1 xenograft tumor of nude mice, making a great promise to improve the precision diagnosis and therapy of pancreatic cancer with real time tracing and bioimaging of PDAC in vitro and in vivo.

Keywords

NIR fluorescence probe NGR aminopeptidase N Caveolin-1 pancreatic ductal adenocarcinoma 

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Notes

Acknowledgments

This work was supported by the National Basic Research Program of China (2013CB733700), the National Natural Science Foundation of China for Creative Research Groups (21421004), Key Project (21636002), and Distinguished Young Scholars (21325625), NSFC/China, the Oriental Scholarship, Science and Technology Commission of Shanghai Municipality (15XD1501400), the Fundamental Research Funds for the Central Universities (222201717003), and Program of Introducing Talents of Discipline to Universities (B16017).

Supplementary material

11426_2017_9092_MOESM1_ESM.pdf (1.2 mb)
cNGR-based synergistic-targeted NIR fluorescent probe for tracing and bioimaging of pancreatic ductal adenocarcinoma

References

  1. 1.
    Singh D, Upadhyay G, Srivastava RK, Shankar S. Biochimica Biophysica Acta (BBA)-Rev Cancer, 2015, 1856: 13–27CrossRefGoogle Scholar
  2. 2.
    Hussain T, Nguyen QT. Adv Drug Deliver Rev, 2014, 66: 90–100CrossRefGoogle Scholar
  3. 3.
    Siegel R, Ma J, Zou Z, Jemal A. CA Cancer J Clin, 2014, 64: 9–29CrossRefPubMedGoogle Scholar
  4. 4.
    Narayanan R. Cancer Genomics Proteomic, 2015, 12: 9–19Google Scholar
  5. 5.
    Maron R, Schechter B, Mancini M, Mahlknecht G, Yarden Y, Sela M. Proc Natl Acad Sci USA, 2013, 110: 15389–15394CrossRefPubMedGoogle Scholar
  6. 6.
    Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, Ramm GA, Buchler M, Friess H, McCarroll JA, Keogh G, Merrett N, Pirola R, Wilson JS. Pancreas, 2004, 29: 179–187CrossRefPubMedGoogle Scholar
  7. 7.
    Saiyin H, Ardito-Abraham CM, Wu Y, Wei Y, Fang Y, Han X, Li J, Zhou P, Yi Q, Maitra A, Liu JO, Tuveson DA, Lou W, Yu L. J Pathol, 2015, 236: 142–154CrossRefGoogle Scholar
  8. 8.
    Bu L, Shen B, Cheng Z. Adv Drug Deliver Rev, 2014, 76: 21–38CrossRefGoogle Scholar
  9. 9.
    Goulart BHL, Clark JW, Lauwers GY, Ryan DP, Grenon N, Muzikansky A, Zhu AX. J Hematol Oncol, 2009, 2: 13CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ducreux M, Boige V, Malka D. Semin Oncol, 2007, 34: S25–S30CrossRefPubMedGoogle Scholar
  11. 11.
    Ge Z, Chen Q, Osada K, Liu X, Tockary TA, Uchida S, Dirisala A, Ishii T, Nomoto T, Toh K, Matsumoto Y, Oba M, Kano MR, Itaka K, Kataoka K. Biomaterials, 2014, 35: 3416–3426CrossRefPubMedGoogle Scholar
  12. 12.
    Ji S, Xu J, Zhang B, Yao W, Xu W, Wu W, Xu Y, Wang H, Ni Q, Hou H, Yu X. Cancer Biol Ther, 2012, 13: 206–215CrossRefPubMedGoogle Scholar
  13. 13.
    Zhou M, Ni QW, Yang SY, Qu CY, Zhao PC, Zhang JC, Xu LM. World J Gastroenterol, 2013, 19: 6559–6567CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li H, Li Y, Cui L, Wang B, Cui W, Li M, Cheng Y. PLoS ONE, 2014, 9: e106566CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Liu F, Le W, Mei T, Wang T, Chen L, Lei Y, Cui S, Chen B, Cui Z, Shao C. Int J Nanomed, 2016, 11: 2195–2207Google Scholar
  16. 16.
    Wang X, Xing X, Zhang B, Liu F, Cheng Y, Shi D. Int J Nanomed, 2014, 9: 1601–1615CrossRefGoogle Scholar
  17. 17.
    Ji T, Li S, Zhang Y, Lang J, Ding Y, Zhao X, Zhao R, Li Y, Shi J, Hao J, Zhao Y, Nie G. ACS Appl Mater Interfaces, 2016, 8: 3438–3445CrossRefPubMedGoogle Scholar
  18. 18.
    Frič P, Škrha J, Šedo A, Zima T, Bušek P, Kmochová K, Laclav M, Bunganič B, Solar S, Hrabal P, Bělina F, Záruba P, Škrha P, Zavoral M. Eur J Gastroen Hepat, 2016, 28: e33–e43CrossRefGoogle Scholar
  19. 19.
    Jamieson NB, Carter CR, McKay CJ, Oien KA. Clin Cancer Res, 2011, 17: 3316–3331CrossRefPubMedGoogle Scholar
  20. 20.
    Grønborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, Molina H, Jensen ON, Hruban RH, Goggins MG, Maitra A, Pandey A. Mol Cell Proteomics, 2006, 5: 157–171CrossRefPubMedGoogle Scholar
  21. 21.
    Tonini G, Pantano F, Vincenzi B, Gabbrielli A, Coppola R, Santini D. Expert Opin Ther Targets, 2007, 11: 1553–1569CrossRefPubMedGoogle Scholar
  22. 22.
    Janky R, Binda MM, Allemeersch J, Van den Broeck A, Govaere O, Swinnen JV, Roskams T, Aerts S, Topal B. BMC Cancer, 2016, 16: 632CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Majhen D, Gabrilovac J, Eloit M, Richardson J, Ambriovic-Ristov A. Biochem Biophysical Res Commun, 2006, 348: 278–287CrossRefGoogle Scholar
  24. 24.
    Colombo G, Curnis F, De Mori GMS, Gasparri A, Longoni C, Sacchi A, Longhi R, Corti A. J Biol Chem, 2002, 277: 47891–47897CrossRefPubMedGoogle Scholar
  25. 25.
    Curnis F, Sacchi A, Gasparri A, Longhi R, Bachi A, Doglioni C, Bordignon C, Traversari C, Rizzardi GP, Corti A. Cancer Res, 2008, 68: 7073–7082CrossRefPubMedGoogle Scholar
  26. 26.
    Aron AT, Loehr MO, Bogena J, Chang CJ. J Am Chem Soc, 2016, 138: 14338–14346CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Murphy S, Bright SA, Poynton FE, McCabe T, Kitchen JA, Veale EB, Williams DC, Gunnlaugsson T. Org Biomol Chem, 2014, 12: 6610–6623CrossRefPubMedGoogle Scholar
  28. 28.
    Takaoka Y, Nishikawa Y, Hashimoto Y, Sasaki K, Hamachi I. Chem Sci, 2015, 6: 3217–3224CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lee MH, Kim EJ, Lee H, Kim HM, Chang MJ, Park SY, Hong KS, Kim JS, Sessler JL. J Am Chem Soc, 2016, 138: 16380–16387CrossRefPubMedGoogle Scholar
  30. 30.
    Chang S, Wu X, Li Y, Niu D, Ma Z, Zhao W, Gu J, Dong W, Ding F, Zhu W, Shi J. Adv Healthcare Mater, 2012, 1: 475–479CrossRefGoogle Scholar
  31. 31.
    Liu C, Yu W, Chen Z, Zhang J, Zhang N. J Control Release, 2011, 151: 162–175CrossRefPubMedGoogle Scholar
  32. 32.
    Meng N, Han L, Pan XH, Su L, Jiang Z, Lin Z, Zhao J, Zhang SL, Zhang Y, Zhao BX, Miao JY. Cell Biol Toxicol, 2015, 31: 15–27CrossRefPubMedGoogle Scholar
  33. 33.
    Midoux P, Breuzard G, Gomez J, Pichon C. Curr Gene Ther, 2008, 8: 335–352CrossRefPubMedGoogle Scholar
  34. 34.
    Mina-Osorio P. Trends Mol Med, 2008, 14: 361–371CrossRefPubMedGoogle Scholar
  35. 35.
    Luan Y, Xu W. Curr Med Chem, 2007, 14: 639–647CrossRefPubMedGoogle Scholar
  36. 36.
    Ikeda N, Nakajima Y, Tokuhara T, Hattori N, Sho M, Kanehiro H, Miyake M. Clin Cancer Res, 2003, 9: 1503–1508PubMedGoogle Scholar
  37. 37.
    Huang C, Qiu Z, Wang L, Peng Z, Jia Z, Logsdon CD, Le X, Wei D, Huang S, Xie K. Cancer Res, 2012, 72: 655–665CrossRefPubMedGoogle Scholar
  38. 38.
    Chatterjee M, Ben-Josef E, Thomas DG, Morgan MA, Zalupski MM, Khan G, Andrew Robinson C, Griffith KA, Chen CS, Ludwig T, Bekaii-Saab T, Chakravarti A, Williams TM. Sci Rep, 2015, 5: 10867CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tanase CP, Dima S, Mihai M, Raducan E, Nicolescu MI, Albulescu L, Voiculescu B, Dumitrascu T, Cruceru LM, Leabu M, Popescu I, Hinescu ME. J Mol Hist, 2009, 40: 23–29CrossRefGoogle Scholar
  40. 40.
    Liu L, Xu HX, Wang WQ, Wu CT, Chen T, Qin Y, Liu C, Xu J, Long J, Zhang B, Xu YF, Ni QX, Li M, Yu XJ. Oncogene, 2014, 33: 2728–2736CrossRefPubMedGoogle Scholar
  41. 41.
    Tanase CP. Expert Rev Mol Diagn, 2008, 8: 395–404CrossRefPubMedGoogle Scholar
  42. 42.
    Han F, Zhu HG. J Surgical Res, 2010, 159: 443–450CrossRefGoogle Scholar
  43. 43.
    Fateminia SMA, Wang Z, Goh CC, Manghnani PN, Wu W, Mao D, Ng LG, Zhao Z, Tang BZ, Liu B. Adv Mater, 2017, 29: 1604100CrossRefGoogle Scholar
  44. 44.
    Yang H, Han C, Zhu X, Liu Y, Zhang KY, Liu S, Zhao Q, Li F, Huang W. Adv Funct Mater, 2016, 26: 1945–1953CrossRefGoogle Scholar
  45. 45.
    Li S, Wang X, Hu R, Chen H, Li M, Wang J, Wang Y, Liu L, Lv F, Liang XJ, Wang S. Chem Mater, 2016, 28: 8669–8675CrossRefGoogle Scholar
  46. 46.
    Fujii T, Kamiya M, Urano Y. Bioconjugate Chem, 2014, 25: 1838–1846CrossRefGoogle Scholar
  47. 47.
    Shao A, Xie Y, Zhu S, Guo Z, Zhu S, Guo J, Shi P, James TD, Tian H, Zhu WH. Angew Chem Int Ed, 2015, 54: 7275–7280CrossRefGoogle Scholar
  48. 48.
    Liang J, Feng G, Kwok RTK, Ding D, Tang B, Liu B. Sci China Chem, 2016, 59: 53–61CrossRefGoogle Scholar
  49. 49.
    Zhou X, Zeng Y, Liyan C, Wu X, Yoon J. Angew Chem Int Ed, 2016, 55: 4729–4733CrossRefGoogle Scholar
  50. 50.
    Li D, Yu J. Small, 2016, 12: 6478–6494CrossRefPubMedGoogle Scholar
  51. 51.
    Gu K, Xu Y, Li H, Guo Z, Zhu S, Zhu S, Shi P, James TD, Tian H, Zhu WH. J Am Chem Soc, 2016, 138: 5334–5340CrossRefPubMedGoogle Scholar
  52. 52.
    Yu Y, Huang Y, Hu F, Jin Y, Zhang G, Zhang D, Zhao R. Anal Chem, 2016, 88: 6374–6381CrossRefPubMedGoogle Scholar
  53. 53.
    Wu X, Shao A, Zhu S, Guo Z, Zhu W. Sci China Chem, 2016, 59: 62–69CrossRefGoogle Scholar
  54. 54.
    Miki K, Kuramochi Y, Oride K, Inoue S, Harada H, Hiraoka M, Ohe K. Bioconjugate Chem, 2009, 20: 511–517CrossRefGoogle Scholar
  55. 55.
    Gladkovskaya O, Gun’ko YK, O’Connor GM, Gogvadze V, Rochev Y. Nanomedicine, 2016, 11: 2603–2615CrossRefPubMedGoogle Scholar
  56. 56.
    Veiseh O, Kievit FM, Liu V, Fang C, Stephen ZR, Ellenbogen RG, Zhang M. Mol Pharm, 2013, 10: 4099–4106CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Su L, Han L, Ge F, Zhang SL, Zhang Y, Zhao BX, Zhao J, Miao JY. J Hazard Mater, 2012, 235-236: 316–325CrossRefPubMedGoogle Scholar
  58. 58.
    Majkova Z, Toborek M, Hennig B. J Cellular Mol Med, 2010, 14: 2359–2370CrossRefGoogle Scholar
  59. 59.
    Cokakli M, Erdal E, Nart D, Yilmaz F, Sagol O, Kilic M, Karademir S, Atabey N. BMC Cancer, 2009, 9: 65CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lacerda L, Pastorin G, Gathercole D, Buddle J, Prato M, Bianco A, Kostarelos K. Adv Mater, 2007, 19: 1480–1484CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Yan Tang
    • 1
  • Andong Shao
    • 2
  • Jun Cao
    • 3
  • Hui Li
    • 1
  • Qiang Li
    • 2
  • Meiying Zeng
    • 1
  • Ming Liu
    • 2
  • Yingsheng Cheng
    • 1
  • Weihong Zhu
    • 2
  1. 1.Department of RadiologyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina
  2. 2.Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina
  3. 3.Department of Interventional OncologyDahua HospitalShanghaiChina

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