Synthesis, MR Relaxivities, and In Vitro Cytotoxicity of 3,5-Diiodo-L-tyrosine-Coated Gd2O3 Nanoparticles

  • Md Wasi AhmadEmail author
  • Mohammad Yaseen Ahmad
  • Mazhar Ul-Islam
  • Wenlong Xu
  • Tirusew Tegafaw
  • Aref A. Wazwaz
  • Ahmmed S. Ibrehem
  • Mohd Shariq Khan
  • In-Taek Oh
  • Kwon Seok Chae
  • Hyunsil Cha
  • Yongmin ChangEmail author
  • Gang Ho LeeEmail author


In this study, we report the synthesis and characterization of 3,5-Diiodo-L-tyrosine (DLT)-coated gadolinium oxide (Gd2O3) nanoparticles. The bonding status of DLT-coated Gd2O3 nanoparticles (DLT-NPs) were confirmed by Fourier transform infrared (FT-IR) absorption spectra and thermogravimetric analysis (TGA). The surface coating amount was estimated to be 73% in weight percent from a TGA. High-resolution transmission electron microscope (HR-TEM) shows that DLT-NPs were spherical in shape with an average diameter 2 nm. The MR relaxivity measurements confirmed that the DLT-NPs have higher r1 = 9.24 s-1 mM-1 than commercially available contrast agents. Furthermore, the bio-compatibility of the DLT-NPs were measured by cytotoxicity test, which has demonstrated that the cell viability reached up to 60% with Gd concentrations up to 50 μM for both DU145 and NCTC1469 cell lines, making them a promising candidate for biomedical applications.


3,5-Diiodo-L-tyrosine Gd2O3 nanoparticles Relaxivities Cytotoxicity 


  1. 1.
    Rohullah, A., Qiao, A., Islam, S., Ali, M. U., Wahab, J., Khan, A., Farhan, M. A., & Hameed, A. (2016). Facile synthesis of hair-extract-capped gold and silver nanoparticles and their biological applications. RSC Advances, 6, 113452–111345. Scholar
  2. 2.
    Khan, M. M., Ansari, S. A., Pradhan, D., Ansari, M. O., Han, D. H., Lee, J., & Cho, M. H. (2014). Band gap engineered TiO2 nanoparticles for visible light induced photoelectrochemical and photocatalytic studies. Journal of Materials Chemistry A, 2, 637–644. Scholar
  3. 3.
    Khan, M. M., Ansari, S. A., Lee, J.-H., Ansari, M. O., Lee, J., Moo, J., & Cho, M. H. (2014). Electrochemically active biofilm assisted synthesis of ag@CeO2 nanocomposites for antimicrobial activity, photocatalysis and photoelectrodes. Journal of Colloid and Interface Science, 431, 255–263. Scholar
  4. 4.
    Khan, M. M., Kalathil, S., Lee, J., & Cho, M. H. (2012). Synthesis of cysteine capped silver nanoparticles by electrochemically active biofilm and their antibacterial activities. Bulletin Korean Chemical Society, 33, 2592–2596. Scholar
  5. 5.
    Ali, N., Awais, Kamal, T., Islam, M. U., Khan, A., Shah, S. J., & Zada, A. (2018). Chitosan-coated cotton cloth supported copper nanoparticles for toxic dye reduction. International Journal of Biological Macromolecules, 111, 832–838. Scholar
  6. 6.
    Khalid, A., Ullah, H., Islam, M. U., Khan, R., Khan, S., Ahmad, F., Khan, T., & Wahid, F. (2017). Bacterial cellulose–TiO2 nanocomposites promote healing and tissue regeneration in burn mice model. RSC Advances, 7, 47662–47668. Scholar
  7. 7.
    Lee, N., & Hyeon, T. (2012). Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chemical Society Reviews, 41, 2575–2589. Scholar
  8. 8.
    Laurent, S., Forge, D., Port, M., Roch, A., Robic, C., Elst, L. V., & Muller, R. N. (2008). Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chemical Reviews, 108, 2064–2110. Scholar
  9. 9.
    Tegafaw, T., Xu, W., Ahmad, M. W., Xu, M., Chang, Y., Chae, K. S., Kim, T. J., & Lee, G. H. (2016). Fluorescent brightener 28-coated Fe3O4 nanoparticles: synthesis, characterization, and fluorescent properties. Journal of Nanoscience and Nanotechnology, 16, 10986–10990. Scholar
  10. 10.
    Baek, M. J., Park, J. Y., Xu, W., Kattel, K., Kim, H. G., Lee, E. J., Patel, A. K., Lee, J. J., Chang, Y., Kim, T. J., Bae, J. E., Chae, K. S., & Lee, G. H. (2010). Water-soluble MnO nanocolloid for a molecular T1 MR imaging: a facile one-pot synthesis, in vivo T1 MR images, and account for relaxivities. ACS Applied Materials & Interfaces, 2, 2949–2955. Scholar
  11. 11.
    Kim, T., Momin, E., Choi, J., Yuan, K., Zaidi, H., Kim, J., Park, M., Lee, N., McMahon, M. T., Quinones-Hinojosa, A., Bulte, J. W. M., Hyeon, T., & Gilad, A. A. (2011). Mesoporous silica-coated hollow manganese oxide nanoparticles as positive T1 contrast agents for labeling and MRI tracking of adipose-derived mesenchymal stem cells. Journal of the American Chemical Society, 133, 2955–2961. Scholar
  12. 12.
    Choi, E. S., Park, J. Y., Baek, M. J., Xu, W., Kattel, K., Kim, J. H., Lee, J. J., Chang, Y., Kim, T. J., Bae, J. E., Chae, K. S., Suh, K. J., & Lee, G. H. (2010). Water-soluble ultra-small manganese oxide surface doped gadolinium oxide (Gd2O3@MnO) nanoparticles for MRI contrast agent. European Journal of Inorganic Chemistry, 2010, 4555–4560. Scholar
  13. 13.
    Ahmad, M. Y., Ahmad, M. Y., Cha, H., Oh, I.-T., Tegafaw, T., Miao, X., Ho, S. L., Marasini, S., Ghazanfari, A., Yue, H., Ryeom, H.-K., Lee, J., Chae, K. S., Chang, Y., & Lee, G. H. (2018). Cyclic RGD-coated ultrasmall Gd2O3 nanoparticles as tumor-targeting positive magnetic resonance imaging contrast agent. European Journal of Inorganic Chemistry, 2018, 3070–3079. Scholar
  14. 14.
    Xu, W., Park, J. Y., Kattel, K., Ahmad, M. W., Bony, B. A., Heo, W. C., Jin, S., Park, J. W., Chang, Y., Kim, T. J., Park, J. A., Do, Y. Y., Chaee, K. S., & Lee, G. H. (2012). Fluorescein-polyethyleneimine coated gadolinium oxide nanoparticles as T1 magnetic resonance imaging (MRI)–cell labeling (CL) dual agents. RSC Advances, 2, 10907–10915. Scholar
  15. 15.
    Tegafaw, T., Xu, W., Ahmad, M. W., Baeck, J. S., Chang, Y., Bae, J. E., Chae, K. S., & Lee, G. H. (2015). Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: Synthesis, characterization, and in vivo application. Nanotechnology, 26, 365102. Scholar
  16. 16.
    Bridot, J.-L., Faure, A.-C., Laurent, S., Riviere, C., Billotey, C., Hiba, B., Janier, M., Josserand, V., Coll, J.-L., Elst, L. V., Muller, R., Roux, S., Perriat, P., & Tillement, O. (2007). Hybrid gadolinium oxide nanoparticles: Multimodal contrast agents for in vivo imaging. Journal of the American Chemical Society, 129, 5076–5084. Scholar
  17. 17.
    Hifumi, H., Yamaoka, S., Tanimoto, A., Citterio, D., & Suzuki, K. (2006). Gadolinium-based hybrid nanoparticles as a positive MR contrast agent. Journal of the American Chemical Society, 128, 15090–15091. Scholar
  18. 18.
    Yoon, Y., Lee, B.-I., Lee, K. S., Heo, H., Lee, J. H., Byeon, S.-H., & Lee, I. S. (2010). Fabrication of a silica sphere with fluorescent and MR contrasting GdPO4 nanoparticles from layered gadolinium hydroxide. Chemical Communications, 46, 3654–3656. Scholar
  19. 19.
    Feldmann, V., Engelmann, J., Gottschalk, S., & Mayer, H. A. (2012). Synthesis, characterization and examination of Gd[DO3A-hexylamine]-functionalized silica nanoparticles as contrast agent for MRI-applications. Journal of Colloid and Interface Science, 366, 70–79. Scholar
  20. 20.
    Cotton, F. A., & Wilkinson, G. (1980). Advanced inorganic chemistry (4th ed.p. 984). New York: A Wiley-Inter science Publication.Google Scholar
  21. 21.
    Lauffer, R. B. (1987). Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: Theory and design. Chemical Reviews, 87, 901–927. Scholar
  22. 22.
    Caravan, P., Ellison, J. J., McMurry, T. J., & Lauffer, R. B. (1999). Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications. Chemical Reviews, 99, 2293–2352. Scholar
  23. 23.
    Park, J. Y., Patel, D., Lee, G. H., Woo, S., & Chang, Y. (2008). Highly water-dispersible PEG surface modified ultrasmall superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications. Nanotechnology, 19, 365603. Scholar
  24. 24.
    Patel, D., Moon, J. Y., Chang, Y., Kim, T. J., & Lee, G. H. (2008). Poly(D,L-lactide-co-glycolide) coated superparamagnetic iron oxide nanoparticles: Synthesis, characterization and in vivo study as MRI contrast agent. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 313-314, 91–94. Scholar
  25. 25.
    Park, J. Y., Baek, M. J., Choi, E. S., Woo, S., Kim, J. H., Kim, T. J., Jung, J. C., Chae, K. S., Chang, Y., & Lee, G. H. (2009). Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images. ACS Nano, 3, 3663–3669. Scholar
  26. 26.
    Kattel, K., Park, J. Y., Xu, W., Kim, H. G., Lee, E. J., Bony, B. A., Heo, W. C., Lee, J. J., Jin, S., Baeck, J. S., Chang, Y., Kim, T. J., Bae, J. E., Chae, K. S., & Lee, G. H. (2011). A facile synthesis, in vitro and in vivo MR studies of D-glucuronic acid-coated ultrasmall Ln2O3 (ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential MRI contrast agent. ACS Applied Materials & Interfaces, 3, 3325–3334. Scholar
  27. 27.
    Xu, W., Park, J. Y., Kattel, K., Bony, B. A., Heo, W. C., Jin, S., Park, J. W., Chang, Y., Do, J. Y., Chae, K. S., Kim, T. J., Park, J. A., Kwak, Y. W., & Lee, G. H. (2012). A T1, T2 magnetic resonance imaging (MRI)-fluorescent imaging (FI) by using ultrasmall mixed gadolinium-europium oxide nanoparticles. New Journal of Chemistry, 36, 2361–2367. Scholar
  28. 28.
    Ahmad, M. W., Xu, W., Kim, S. J., Baeck, J. S., Chang, Y., Bae, J. E., Chae, K. S., Park, J. A., Kim, T. J., & Lee, G. H. (2015). Potential dual imaging nanoparticles: Gd2O3 nanoparticle. Scientific Reports, 5, 8549. Scholar
  29. 29.
    Card number 43-1014, PCPDFWIN, Version 1.30, 1997.Google Scholar
  30. 30.
    Duckworth, O. W., & Martin, S. T. (2001). Surface complexation and dissolution of hematite by C1-C6 dicarboxylic acids at pH = 5.0. Geochimica et Cosmochimica Acta, 65, 4289–4301. Scholar
  31. 31.
    Hug, S. J., & Bahnemann, D. (2006). Infrared spectra of oxalate, malonate and succinate adsorbed on the aqueous surface of rutile, anatase and lepidocrocite measured with in situ ATR-FTIR. Journal of Electron Spectroscopy and Related Phenomena, 150, 208–219. Scholar
  32. 32.
    Hug, S. J., & Sulzberger, B. (1994). In situ Fourier transform infrared spectroscopic evidence for the formation of several different surface complexes of oxalate on TiO2 in the aqueous phase. Langmuir, 10, 3587–3597. Scholar
  33. 33.
    Mendive, C. B., Bredow, T., Blesa, M. A., & Bahnemann, D. W. (2006). ATR-FTIR measurements and quantum chemical calculations concerning the adsorption and photoreaction of oxalic acid on TiO2. Physical Chemistry Chemical Physics, 8, 3232–3247. Scholar
  34. 34.
    Lal, H. B., Pratap, V., & Kumar, A. (1978). Magnetic susceptibility of heavy rare-earth sesquioxides. Pramana Journal of Physics, 10, 409–412. Scholar
  35. 35.
    Choi, H. S., Liu, W., Misra, P., Tanaka, E., Zimmer, J. P., Ipe, B. I., Bawendi, M. G., & Frangioni, J. V. (2007). Renal clearance of quantum dots. Nature Biotechnology, 25, 1165–1170. Scholar
  36. 36.
    Ahmad, M. W., Kim, C. R., Baeck, J. S., Chang, Y., Kim, T. J., Bae, J. E., Chae, K. S., & Lee, G. H. (2014). Bovine serum albumin (BSA) and cleaved-BSA conjugated ultrasmall Gd2O3 nanoparticles: synthesis, characterization, and application to MRI contrast agents. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 450, 67–75. Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Md Wasi Ahmad
    • 1
    Email author
  • Mohammad Yaseen Ahmad
    • 2
  • Mazhar Ul-Islam
    • 1
  • Wenlong Xu
    • 2
  • Tirusew Tegafaw
    • 2
  • Aref A. Wazwaz
    • 1
  • Ahmmed S. Ibrehem
    • 1
  • Mohd Shariq Khan
    • 1
  • In-Taek Oh
    • 3
  • Kwon Seok Chae
    • 3
  • Hyunsil Cha
    • 4
  • Yongmin Chang
    • 4
    Email author
  • Gang Ho Lee
    • 2
    Email author
  1. 1.Department of Chemical EngineeringDhofar UniversitySalalahSultanate of Oman
  2. 2.Department of Chemistry, College of Natural SciencesKyungpook National University (KNU)TaeguSouth Korea
  3. 3.Department of Biology Education, Teacher’s CollegeKNUTaeguSouth Korea
  4. 4.Department of Molecular Medicine and Medical & Biological Engineering, School of MedicineTaeguSouth Korea

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