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Science China Chemistry

, Volume 61, Issue 9, pp 1110–1122 | Cite as

Recent advances on stimuli-responsive macromolecular magnetic resonance imaging (MRI) contrast agents

  • Jinming Hu
  • Shiyong Liu
Feature Articles
  • 34 Downloads

Abstract

Magnetic resonance imaging (MRI) has been extensively used in clinical diagnosis and currently over 30% MRI runs are performed in the presence of contrast agents. However, commercially available contrast agents originated from small molecules typically exhibit relatively low relaxivities and insufficient circulation time. Therefore, there is a long pursuit to develop new contrast agents with high relaxivities to discriminate pathological tissues from normal ones. Compared with small molecule MRI contrast agents, the incorporation of small molecule contrast agents into macromolecular scaffolds allows for constructing macromolecular MRI contrast agents, remarkably elevating the relaxivities due in part to increased rotational correlation time (τR). Moreover, if the macromolecular scaffolds are responsive to external stimuli, the MRI signals could be selectively switched on at the desired sites (e.g., pathological tissues), further intensifying the imaging contrast. In this feature article, we outline the recent achievements in the fabrication of stimuli-responsive macromolecular MRI contrast agents. Specifically, macromolecular contrast agents being responsive to acidic pH, redox potentials, and other stimuli including photoirradiation, pathogens, and salt concentration are discussed. These smart contrast agents could affect either longitudinal (T1) or transverse (T2) relaxation times of water protons or other nuclei (e.g., 19F), exhibiting enhanced signals in pathological tissues yet suppressed signals in normal ones and displaying promising potentials in in vitro and in vivo MRI applications.

Keywords

pH-responsive redox-responsive contrast agents magnetic resonance imaging 

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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (51690150, 51690154, 21674103, 51722307, 51673179), the International S&T Cooperation Program of China (ISTCP) of MOST (2016YFE0129700), the Natural Science Foundation of Anhui Province (1708085QB34), and the Fundamental Research Funds for the Central Universities (WK3450000003, WK2060200023).

References

  1. 1.
    De Leon-Rodriguez LM, Lubag AJM, Malloy CR, Martinez GV, Gillies RJ, Sherry AD. Acc Chem Res, 2009, 42: 948–957CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sherry AD, Wu Y. Curr Opin Chem Biol, 2013, 17: 167–174CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Major JL, Meade TJ. Acc Chem Res, 2009, 42: 893–903CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Davies GL, Kramberger I, Davis JJ. Chem Commun, 2013, 49: 9704–9721CrossRefGoogle Scholar
  5. 5.
    Tang J, Sheng Y, Hu H, Shen Y. Prog Polym Sci, 2013, 38: 462–502CrossRefGoogle Scholar
  6. 6.
    Liu T, Qian Y, Hu X, Ge Z, Liu S. J Mater Chem, 2012, 22: 5020–5030CrossRefGoogle Scholar
  7. 7.
    Hu J, Qian Y, Wang X, Liu T, Liu S. Langmuir, 2012, 28: 2073–2082CrossRefPubMedGoogle Scholar
  8. 8.
    Li Y, Qian Y, Liu T, Zhang G, Hu J, Liu S. Polym Chem, 2014, 5: 1743–1750CrossRefGoogle Scholar
  9. 9.
    Sun X, Xu J, Tang J, Sui M, Shen Y. Chin J Polym Sci, 2011, 29: 427–430CrossRefGoogle Scholar
  10. 10.
    Hu C, Xia T, Gong Y, Wang X, Liu R, Zhang Q, Yi C, Xu Z, Guo D. Chin J Polym Sci, 2016, 34: 135–146CrossRefGoogle Scholar
  11. 11.
    Du H, Shen Y, Liu Y, Han L, Zheng Y, Yan G, Tu Y, Wu J, Guo Q, Zhang Y, Xia X, Lan X, Zhang Y. Chin J Polym Sci, 2015, 33: 1325–1333CrossRefGoogle Scholar
  12. 12.
    Hu J, Liu S. Sci China Chem, 2017, 60: 1153–1161CrossRefGoogle Scholar
  13. 13.
    Li X, Qian Y, Liu T, Hu X, Zhang G, You Y, Liu S. Biomaterials, 2011, 32: 6595–6605CrossRefPubMedGoogle Scholar
  14. 14.
    Liu T, Li X, Qian Y, Hu X, Liu S. Biomaterials, 2012, 33: 2521–2531CrossRefPubMedGoogle Scholar
  15. 15.
    Liu T, Zhang Y, Liu S. Chin J Polym Sci, 2013, 31: 924–937CrossRefGoogle Scholar
  16. 16.
    Qi MW, Huang W, Xiao GY, Zhu XY, Gao C, Zhou YF. Acta Polym Sin, 2017, 2: 214–228Google Scholar
  17. 17.
    Wang LH, Hong CY. Acta Polym Sin, 2017, 2: 200–213Google Scholar
  18. 18.
    Cheng YY. Acta Polym Sin, 2017, 8: 1234–1245Google Scholar
  19. 19.
    Huang Y, Wang ST, Zhu XY. Acta Polym Sin, 2017, 245–258Google Scholar
  20. 20.
    Yu X, Gong L, Zhang J, Zhao Z, Zhang X, Tan W. Sci China Chem, 2017, 60: 1318–1323CrossRefGoogle Scholar
  21. 21.
    Wu S, Li J, Liang H, Wang L, Chen X, Jin G, Xu X, Yang HH. Sci China Chem, 2017, 60: 628–634CrossRefGoogle Scholar
  22. 22.
    Wang W, Ma X, Yu X. Chin J Polym Sci, 2017, 35: 1352–1362CrossRefGoogle Scholar
  23. 23.
    Lu X, Yang X, Meng Y, Li S. Chin J Polym Sci, 2017, 35: 534–546CrossRefGoogle Scholar
  24. 24.
    Zheng XX, Lin H, Wang LQ. Acta Polym Sin, 2017, 11: 1789–1795Google Scholar
  25. 25.
    Feng X, Ding J, Gref R, Chen X. Chin J Polym Sci, 2017, 35: 693–699CrossRefGoogle Scholar
  26. 26.
    Li Q, Li L, Wang H, Wang R, Wang W, Jiang Y, Tian Q, Liu J. Chin J Polym Sci, 2017, 35: 66–77CrossRefGoogle Scholar
  27. 27.
    Miao H, Wang Y, Dong H, Chen D. Chin J Polym Sci, 2017, 35: 46–53CrossRefGoogle Scholar
  28. 28.
    Yang J, Ren L, Li Y. Chin J Polym Sci, 2017, 35: 36–45CrossRefGoogle Scholar
  29. 29.
    Zhang Y, Li M, Li Z, Li Q, Aldalbahi A, Shi J, Wang L, Fan C, Zuo X. Sci China Chem, 2017, 60: 1474–1480CrossRefGoogle Scholar
  30. 30.
    Du J, Zhang X, Yan L, Chen R. Sci China Chem, 2017, 60: 1425–1438CrossRefGoogle Scholar
  31. 31.
    Ding Y, Hu Y, Wu W, Jiang XQ. Sci China Chem, 2010, 53: 479–486CrossRefGoogle Scholar
  32. 32.
    Wang LH, Zhang Z, Zeng TY, Xia L, Nie X, Chen G, You YZ. Acta Polym Sin, 2017, 12: 1883–1904Google Scholar
  33. 33.
    Xu J, Ge Z, Zhu Z, Luo S, Liu H, Liu S. Macromolecules, 2006, 39: 8178–8185CrossRefGoogle Scholar
  34. 34.
    Yin J, Hu H, Wu Y, Liu S. Polym Chem, 2011, 2: 363–371CrossRefGoogle Scholar
  35. 35.
    Xu J, Liu S. J Polym Sci A Polym Chem, 2009, 47: 404–419CrossRefGoogle Scholar
  36. 36.
    Jiang X, Zhang G, Narain R, Liu S. Langmuir, 2009, 25: 2046–2054CrossRefPubMedGoogle Scholar
  37. 37.
    Li YM, Liu SY. Acta Polym Sin, 2017, 7: 1178–1190Google Scholar
  38. 38.
    Stephen ZR, Kievit FM, Zhang M. Mater Today, 2011, 14: 330–338CrossRefGoogle Scholar
  39. 39.
    Li L, Jiang W, Luo K, Song H, Lan F, Wu Y, Gu Z. Theranostics, 2013, 3: 595–615CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Shen Z, Wu A, Chen X. Mol Pharm, 2017, 14: 1352–1364CrossRefPubMedGoogle Scholar
  41. 41.
    Ge Z, Liu S. Chem Soc Rev, 2013, 42: 7289–7325CrossRefPubMedGoogle Scholar
  42. 42.
    Li C, Zhang Y, Hu J, Cheng J, Liu S. Angew Chem Int Ed, 2010, 49: 5120–5124CrossRefGoogle Scholar
  43. 43.
    Li Y, Liu G, Wang X, Hu J, Liu S. Angew Chem Int Ed, 2016, 55: 1760–1764CrossRefGoogle Scholar
  44. 44.
    Liu G, Shi G, Sheng H, Jiang Y, Liang H, Liu S. Angew Chem Int Ed, 2017, 56: 8686–8691CrossRefGoogle Scholar
  45. 45.
    Wang X, Liu G, Hu J, Zhang G, Liu S. Angew Chem Int Ed, 2014, 53: 3138–3142CrossRefGoogle Scholar
  46. 46.
    Deng Z, Qian Y, Yu Y, Liu G, Hu J, Zhang G, Liu S. J Am Chem Soc, 2016, 138: 10452–10466CrossRefPubMedGoogle Scholar
  47. 47.
    Hu X, Hu J, Tian J, Ge Z, Zhang G, Luo K, Liu S. J Am Chem Soc, 2013, 135: 17617–17629CrossRefPubMedGoogle Scholar
  48. 48.
    Hu X, Liu G, Li Y, Wang X, Liu S. J Am Chem Soc, 2015, 137: 362–368CrossRefPubMedGoogle Scholar
  49. 49.
    Liu G, Wang X, Hu J, Zhang G, Liu S. J Am Chem Soc, 2014, 136: 7492–7497CrossRefPubMedGoogle Scholar
  50. 50.
    Liu G, Zhang G, Hu J, Wang X, Zhu M, Liu S. J Am Chem Soc, 2015, 137: 11645–11655CrossRefPubMedGoogle Scholar
  51. 51.
    Wang X, Hu J, Liu G, Tian J, Wang H, Gong M, Liu S. J Am Chem Soc, 2015, 137: 15262–15275CrossRefPubMedGoogle Scholar
  52. 52.
    Wang X, Hu J, Zhang G, Liu S. J Am Chem Soc, 2014, 136: 9890–9893CrossRefPubMedGoogle Scholar
  53. 53.
    Yu G, Han C, Zhang Z, Chen J, Yan X, Zheng B, Liu S, Huang F. J Am Chem Soc, 2012, 134: 8711–8717CrossRefPubMedGoogle Scholar
  54. 54.
    Meng F, Ni Y, Ji S, Fu X, Wei Y, Sun J, Li Z. Chin J Polym Sci, 2017, 35: 1243–1252CrossRefGoogle Scholar
  55. 55.
    Gao YJ, Qiao ZY, Wang H. Sci China Chem, 2016, 59: 991–1002CrossRefGoogle Scholar
  56. 56.
    Aime S, Crich SG, Botta M, Giovenzana G, Palmisano G, Sisti M. Chem Commun, 1999, 1577–1578Google Scholar
  57. 57.
    Okada S, Mizukami S, Kikuchi K. ChemBioChem, 2010, 11: 785–787CrossRefPubMedGoogle Scholar
  58. 58.
    Viger ML, Sankaranarayanan J, de Gracia Lux C, Chan M, Almutairi A. J Am Chem Soc, 2013, 135: 7847–7850CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhang S, Zhou K, Huang G, Takahashi M, Dean Sherry A, Gao J. Chem Commun, 2013, 49: 6418–6420CrossRefGoogle Scholar
  60. 60.
    Huang X, Huang G, Zhang S, Sagiyama K, Togao O, Ma X, Wang Y, Li Y, Soesbe TC, Sumer BD, Takahashi M, Sherry AD, Gao J. Angew Chem Int Ed, 2013, 52: 8074–8078CrossRefGoogle Scholar
  61. 61.
    Okada S, Mizukami S, Kikuchi K. Bioorg Med Chem, 2012, 20: 769–774CrossRefPubMedGoogle Scholar
  62. 62.
    Hu J, Liu T, Zhang G, Jin F, Liu S. Macromol Rapid Commun, 2013, 34: 749–758CrossRefPubMedGoogle Scholar
  63. 63.
    Schopf E, Sankaranarayanan J, Chan M, Mattrey R, Almutairi A. Mol Pharm, 2012, 9: 1911–1918CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Quinn JF, Whittaker MR, Davis TP. Polym Chem, 2017, 8: 97–126CrossRefGoogle Scholar
  65. 65.
    Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z. J Control Release, 2011, 152: 2–12CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Deng ZY, Hu JM, Liu SY. Macromol Rapid Commun, 2017, 38: 1600685CrossRefGoogle Scholar
  67. 67.
    Huo M, Yuan J, Tao L, Wei Y. Polym Chem, 2014, 5: 1519–1528CrossRefGoogle Scholar
  68. 68.
    Do QN, Ratnakar JS, Kovács Z, Sherry AD. ChemMedChem, 2014, 9: 1116–1129CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Gløgård C, Stensrud G, Aime S. Magn Reson Chem, 2003, 41: 585–588CrossRefGoogle Scholar
  70. 70.
    Lu ZR, Wu X. Isr J Chem, 2010, 50: 220–232CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lu ZR, Wang X, Parker DL, Goodrich KC, Buswell HR. Bioconjugate Chem, 2003, 14: 715–719CrossRefGoogle Scholar
  72. 72.
    Lu ZR, Parker DL, Goodrich KC, Wang X, Dalle JG, Buswell HR. Magn Reson Med, 2004, 51: 27–34CrossRefPubMedGoogle Scholar
  73. 73.
    Zong Y, Wang X, Jeong EK, Parker DL, Lu ZR. Magn Reson Imag, 2009, 27: 503–511CrossRefGoogle Scholar
  74. 74.
    Liu B, Wang D, Liu Y, Zhang Q, Meng L, Chi H, Shi J, Li G, Li J, Zhu X. Polym Chem, 2015, 6: 3460–3471CrossRefGoogle Scholar
  75. 75.
    Zhang M, Song CC, Su S, Du FS, Li ZC. ACS Appl Mater Interfaces, 2018, 10: 7798–7810CrossRefPubMedGoogle Scholar
  76. 76.
    Qiu FY, Zhang M, Du FS, Li ZC. Macromolecules, 2017, 50: 23–34CrossRefGoogle Scholar
  77. 77.
    Qiu FY, Song CC, Zhang M, Du FS, Li ZC. ACS Macro Lett, 2015, 4: 1220–1224CrossRefGoogle Scholar
  78. 78.
    Sowers MA, McCombs JR, Wang Y, Paletta JT, Morton SW, Dreaden EC, Boska MD, Ottaviani MF, Hammond PT, Rajca A, Johnson JA. Nat Commun, 2014, 5: 5460CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Loving GS, Mukherjee S, Caravan P. J Am Chem Soc, 2013, 135: 4620–4623CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Boros E, Gale EM, Caravan P. Dalton Trans, 2015, 44: 4804–4818CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Zhu C, Ninh C, Bettinger CJ. Biomacromolecules, 2014, 15: 3474–3494CrossRefPubMedGoogle Scholar
  82. 82.
    Tomatsu I, Peng K, Kros A. Adv Drug Deliver Rev, 2011, 63: 1257–1266CrossRefGoogle Scholar
  83. 83.
    Gohy JF, Zhao Y. Chem Soc Rev, 2013, 42: 7117–7129CrossRefPubMedGoogle Scholar
  84. 84.
    Liu G, Liu W, Dong CM. Polym Chem, 2013, 4: 3431–3443CrossRefGoogle Scholar
  85. 85.
    Liu G, Dong CM. Biomacromolecules, 2012, 13: 1573–1583CrossRefPubMedGoogle Scholar
  86. 86.
    Zhao H, Sterner ES, Coughlin EB, Theato P. Macromolecules, 2012, 45: 1723–1736CrossRefGoogle Scholar
  87. 87.
    Liu Q, Song L, Chen S, Gao J, Zhao P, Du J. Biomaterials, 2017, 114: 23–33CrossRefPubMedGoogle Scholar
  88. 88.
    Ren T, Liu Q, Lu H, Liu H, Zhang X, Du J. J Mater Chem, 2012, 22: 12329–12338CrossRefGoogle Scholar
  89. 89.
    Ai H, Flask C, Weinberg B, Shuai XT, Pagel MD, Farrell D, Duerk J, Gao J. Adv Mater, 2005, 17: 1949–1952CrossRefGoogle Scholar
  90. 90.
    Gao GH, Im GH, Kim MS, Lee JW, Yang J, Jeon H, Lee JH, Lee DS. Small, 2010, 6: 1201–1204CrossRefPubMedGoogle Scholar
  91. 91.
    Zhu K, Deng Z, Liu G, Hu J, Liu S. Macromolecules, 2017, 50: 1113–1125CrossRefGoogle Scholar
  92. 92.
    Li Y, Yu H, Qian Y, Hu J, Liu S. Adv Mater, 2014, 26: 6734–6741CrossRefPubMedGoogle Scholar
  93. 93.
    Zhang C, Moonshi SS, Peng H, Puttick S, Reid J, Bernardi S, Searles DJ, Whittaker AK. ACS Sens, 2016, 1: 757–765CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and EngineeringUniversity of Science and Technology of ChinaHefeiChina

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