Apatite Coating of Iron Oxide Nanoparticles by Alternate Addition of Calcium and Phosphate Solutions: A Calcium and Carboxylate (Ca-COO) Complex-Mediated Apatite Deposition

  • Vincent Irawan
  • Masaki Takeguchi
  • Toshiyuki IkomaEmail author


Apatite is a biocompatible material widely used to encapsulate iron-oxide nanoparticles (IONPs) for biomedical applications, such as drug-delivery or fluorescent probe agent. Apatite-coated IONPs are commonly fabricated by initially incubating carboxylate-functionalized IONPs in calcium solution and directly adding phosphate solution to initiate apatite precipitation (direct-addition method). Apatite precipitation took place not only on IONPs surface but also in the bulk solution, resulting in apatite-IONPs mixture instead of coated structure. In this study, robust apatite-coated IONPs structure were aimed by modifying steps in direct-addition method. Initially, carboxylate-functionalized IONPs were incubated in calcium solution, physically separated from the incubating calcium solution by external magnet, and then separately reacted with phosphate solution to induce apatite deposition (alternate-addition method). Fourier-transform infrared (FTIR) analysis showed that a calcium solution at a concentration of 0.8 mol/L was required to initiate the formation of the calcium-carboxylate (Ca-COO) complex. The formation of non-stoichiometric apatite was confirmed for IONPs with Ca-COO complex, as evidenced by X-ray diffraction and FTIR analysis. The alternate-addition method produced apatite coating in the form of flake-like structures, which also exhibited strong adhesion to IONPs surface. In contrast, direct-addition method mainly produced agglomerate of apatite particles that weakly associated with IONPs. Both of apatite-coating methods did not alter the magnetic properties of IONPs. The simple modification of reaction steps in the widely used apatite-coating method was demonstrated to be beneficial in producing robust apatite-coated IONPs structure.


Apatite coating Calcium-carboxylate complex Iron oxide nanoparticles 


Supplementary material

10904_2019_1255_MOESM1_ESM.tif (467 kb)
Supplementary material 1 Supplementary Figure 1 Schematic representation of direct-addition and alternate-addition method (TIFF 467 kb)
10904_2019_1255_MOESM2_ESM.tif (1.7 mb)
Supplementary material 2 Supplementary Figure 2 (left figure) Selected area of CaP-0.8 is indicated by yellow box; (right figures) RGB map is a combined image of separate elemental mapping of Fe, Ca, O, and P (TIFF 1690 kb)


  1. 1.
    N. Abbasi Aval, J. Pirayesh Islamian, M. Hatamian, M. Arabfirouzjaei, J. Javadpour, M.R. Rashidi, Int. J. Pharm. 509, 159 (2016)CrossRefGoogle Scholar
  2. 2.
    Q. Wang, B. Chen, F. Ma, S. Lin, M. Cao, Y. Li, N. Gu, Nano Res. 10, 626 (2017)CrossRefGoogle Scholar
  3. 3.
    A.K. Gupta, R.R. Naregalkar, V.D. Vaidya, M. Gupta, Nanomedicine 2, 23 (2007)CrossRefGoogle Scholar
  4. 4.
    D. Bobo, K.J. Robinson, J. Islam, K.J. Thurecht, S.R. Corrie, Pharm. Res. 33, 2373 (2016)CrossRefGoogle Scholar
  5. 5.
    R.M. Patil, N.D. Thorat, P.B. Shete, P.A. Bedge, S. Gavde, M.G. Joshi, S.A.M. Tofail, R.A. Bohara, Biochem. Biophys. Rep. 13, 63 (2018)Google Scholar
  6. 6.
    N. Sadeghiani, L.S. Barbosa, L.P. Silva, R.B. Azevedo, P.C. Morais, Z.G.M. Lacava, J. Magn. Magn. Mater. 289, 466 (2005)CrossRefGoogle Scholar
  7. 7.
    N. Singh, G.J.S. Jenkins, R. Asadi, S.H. Doak, Nano Rev. 1, 5358 (2010)CrossRefGoogle Scholar
  8. 8.
    C.C. Berry, S. Wells, S. Charles, A.S.G. Curtis, Biomaterials 24, 4551 (2003)CrossRefGoogle Scholar
  9. 9.
    M. Mahmoudi, A. Simchi, M. Imani, M.A. Shokrgozar, A.S. Milani, U.O. Häfeli, P. Stroeve, Coll. Surf. B 75, 300 (2010)CrossRefGoogle Scholar
  10. 10.
    S.M. Moghimi, A.C. Hunter, J.C. Murray, Pharmacol. Rev. 53, 283 (2001)Google Scholar
  11. 11.
    E.B. Ansar, M. Ajeesh, Y. Yokogawa, W. Wunderlich, H. Varma, J. Am. Ceram. Soc. 95, 2695 (2012)CrossRefGoogle Scholar
  12. 12.
    S. Karthi, G.A. Kumar, D.K. Sardar, G.C. Dannangoda, K.S. Martirosyan, E.K. Girija, Mater. Chem. Phys. 193, 356 (2017)CrossRefGoogle Scholar
  13. 13.
    N. Tran, T.J. Webster, Acta Biomater. 7, 1298 (2011)CrossRefGoogle Scholar
  14. 14.
    C. Huang, Y. Zhou, Z. Tang, X. Guo, Z. Qian, S. Zhou, Dalt. Trans. 40, 5026 (2011)CrossRefGoogle Scholar
  15. 15.
    M.-H. Chen, T. Yoshioka, T. Ikoma, N. Hanagata, F.-H. Lin, J. Tanaka, Sci. Technol. Adv. Mater. 15, 1 (2016)Google Scholar
  16. 16.
    M. Okuda, M. Takeguchi, Ó.Ó. Ruairc, M. Tagaya, Y. Zhu, A. Hashimoto, N. Hanagata, W. Schmitt, T. Ikoma, J. Electron. Microsc. 59, 173 (2010)CrossRefGoogle Scholar
  17. 17.
    G.K. Toworfe, R.J. Composto, I.M. Shapiro, P. Ducheyne, Biomaterials 27, 631 (2006)CrossRefGoogle Scholar
  18. 18.
    V. Irawan, T. Sugiyama, T. Ikoma, Key Eng. Mater. 696, 121 (2016)CrossRefGoogle Scholar
  19. 19.
    S.K. Papageorgiou, E.P. Kouvelos, E.P. Favvas, A.A. Sapalidis, G.E. Romanos, F.K. Katsaros, Carbohydr. Res. 345, 469 (2010)CrossRefGoogle Scholar
  20. 20.
    X. Gao, D.W. Metge, C. Ray, R.W. Harvey, J. Chorover, Environ. Sci. Technol. 43, 7423 (2009)CrossRefGoogle Scholar
  21. 21.
    H. Zhang, K. Zhou, Z. Li, S. Huang, J. Phys. Chem. Solids 70, 243 (2009)CrossRefGoogle Scholar
  22. 22.
    P. Caesario, T. Harumoto, Y. Nakamura, J. Shi, J. Magn. Magn. Mater. 443, 22 (2017)CrossRefGoogle Scholar
  23. 23.
    M. Răcuciu, D.E. Creangă, A. Airinei, Eur. Phys. J. E 21, 117 (2006)CrossRefGoogle Scholar
  24. 24.
    Y. Sahoo, A. Goodarzi, M.T. Swihart, T.Y. Ohulchanskyy, N. Kaur, E.P. Furlani, P.N. Prasad, J. Phys. Chem. B 109, 3879 (2005)CrossRefGoogle Scholar
  25. 25.
    M. Yamaura, R.L. Camilo, L.C. Sampaio, M.A. Macêdo, M. Nakamura, H.E. Toma, J. Magn. Magn. Mater. 279, 210 (2004)CrossRefGoogle Scholar
  26. 26.
    S. Nigam, K.C. Barick, D. Bahadur, J. Magn. Magn. Mater. 323, 237 (2011)CrossRefGoogle Scholar
  27. 27.
    E. Tombácz, K. Farkas, I. Földesi, M. Szekeres, E. Illés, I.Y. Tóth, D. Nesztor, T. Szabó, Interface Focus 6, 20160068 (2016)CrossRefGoogle Scholar
  28. 28.
    M.E. De Sousa, M.B. Fernández Van Raap, P.C. Rivas, P. Mendoza Zélis, P. Girardin, G.A. Pasquevich, J.L. Alessandrini, D. Muraca, F.H. Sánchez, J. Phys. Chem C 117, 5436 (2013)CrossRefGoogle Scholar
  29. 29.
    K. Nakamoto, in Handbook of Vibrational Spectroscopy, ed. by P.R. Griffiths (Wiley, Chichester, 2006)Google Scholar
  30. 30.
    M.J. Avena, L.K. Koopal, Environ. Sci. Technol. 32, 2572 (1998)CrossRefGoogle Scholar
  31. 31.
    W.C. Miles, P.P. Huffstetler, J.D. Goff, A.Y. Chen, J.S. Riffle, R.M. Davis, Langmuir 27, 5456 (2011)CrossRefGoogle Scholar
  32. 32.
    C. Kotsmar, K.Y. Yoon, H. Yu, S.Y. Ryoo, J. Barth, S. Shao, M. Prodanović, T.E. Milner, S.L. Bryant, C. Huh, K.P. Johnston, Ind. Eng. Chem. Res. 49, 12435 (2010)CrossRefGoogle Scholar
  33. 33.
    E. Tombácz, I.Y. Tóth, D. Nesztor, E. Illés, A. Hajdú, M. Szekeres, L. Vékás, Coll. Surf. A 435, 91 (2013)CrossRefGoogle Scholar
  34. 34.
    T. Taguchi, A. Kishida, M. Akashi, Chem. Lett. 27, 711 (1998)CrossRefGoogle Scholar
  35. 35.
    M. Tanahashi, T. Matsuda, J. Biomed. Mater. Res. 34, 305 (1997)CrossRefGoogle Scholar
  36. 36.
    S. Rhee, J. Tanaka, Biomaterials 20, 2155 (1999)CrossRefGoogle Scholar
  37. 37.
    Y. Lu, J.D. Miller, J. Coll. Interface Sci. 256, 41 (2002)CrossRefGoogle Scholar
  38. 38.
    J.P. Glusker, Acc. Chem. Res. 13, 345 (1980)CrossRefGoogle Scholar
  39. 39.
    E.G. De Araújo, F.E. De Morais, E.V. Dos Santos, C.A. Martinez-Huitle, M.L. Da Silva, S.P.M. Cabral de Souza, N.S. Fernandes, Brazilian. J. Therm. Anal. 2, 17 (2014)CrossRefGoogle Scholar
  40. 40.
    S. Koutsopoulos, J. Biomed. Mater. Res. 62, 600 (2002)CrossRefGoogle Scholar
  41. 41.
    J. Mahamid, A. Sharir, L. Addadi, S. Weiner, Proc. Natl. Acad. Sci. 105, 12748 (2008)CrossRefGoogle Scholar
  42. 42.
    J.D. Termine, A.S. Posner, Nature 211, 268 (1966)CrossRefGoogle Scholar
  43. 43.
    S. Mann, Nature 332, 119 (1988)CrossRefGoogle Scholar
  44. 44.
    M. Kamitakahara, N. Ito, S. Murakami, N. Watanabe, K. Ioku, J. Ceram. Soc. Japan 117, 385 (2009).CrossRefGoogle Scholar
  45. 45.
    Q.J. He, Z.L. Huang, Cryst. Res. Technol. 42, 460 (2007)CrossRefGoogle Scholar
  46. 46.
    K. Hata, T. Kokubo, T. Nakamura, T. Yamamuro, J. Am. Ceram. Soc. 78, 1049 (1995)CrossRefGoogle Scholar
  47. 47.
    A. Narayanaswamy, H. Xu, N. Pradhan, M. Kim, X. Peng, J. Am. Chem. Soc. 128, 10310 (2006)CrossRefGoogle Scholar
  48. 48.
    V. Irawan, T.-C. Sung, A. Higuchi, T. Ikoma, Tissue Eng. Regen. Med. 15, 673 (2018)CrossRefGoogle Scholar
  49. 49.
    A. Ethirajan, U. Ziener, K. Landfester, Chem. Mater. 21, 2218 (2009)CrossRefGoogle Scholar
  50. 50.
    M. Stoia, R. Istratie, C. Păcurariu, J. Therm. Anal. Calorim. 125, 1185 (2016)CrossRefGoogle Scholar
  51. 51.
    I. Tang, N. Krishnamra, N. Charoenphandhu, R. Hoonsawat, W. Pon-On, Nanoscale Res. Lett. 1, 19 (2010)Google Scholar
  52. 52.
    R. Karunamoorthi, G. Suresh Kumar, A.I. Prasad, R.K. Vatsa, A. Thamizhavel, E.K. Girija, J. Am. Ceram. Soc. 97, 1115 (2014)CrossRefGoogle Scholar
  53. 53.
    W.M. Li, S.Y. Chen, D.M. Liu, Acta Biomater. 9, 5360 (2013)CrossRefGoogle Scholar
  54. 54.
    Y. Ling, K. Wei, Y. Luo, X. Gao, S. Zhong, Biomaterials 32, 7139 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Materials Science and Engineering, School of Materials and Chemical TechnologyTokyo Institute of TechnologyTokyoJapan
  2. 2.National Institute of Materials ScienceTsukubaJapan

Personalised recommendations