Highly Luminescent Hydroxyapatite Nanoparticles Hybridized with Citric Acid for Their Bifunctional Cell-Labeling and Cytostatic Suppression Properties

Takuya Kataoka, Sadaki Samitsu, Mitsuhiro Okuda, Daisuke Kawagoe, Motohiro Tagaya

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


We successfully prepared hybrid nanoparticles (NPs) with photofunctional interfaces between the citric acid (Cit) molecules and europium(III) ion (Eu3+)-doped hydroxyapatite (HA) (Eu:HA) to provide bifunctional cell-labeling and cytostatic suppression. In particular, the Eu:HA NPs were synthesized in the presence of Cit, and the Cit molecules were hybridized with the Eu:HA NPs (Cit/Eu:HA). The physicochemical properties based on the interfacial Eu:HA-Cit interactions in the NPs were elucidated. The atomic structures on the Eu:HA NP surface layers were disordered by increasing the liquid-solid interfaces by the interactions between the Cit molecules and the Ca site of Eu:HA NPs. It was suggested that the Cit molecules that interacted with the Eu:HA NP surfaces sterically hindered the NP growth by the inorganic-organic interactions. Moreover, it was demonstrated that the interactions of Cit as an organic molecule and Eu:HA as an inorganic matrix were important for achieving the efficient photoluminescence properties. Thus, the efficient luminescence ability including the internal efficiency for cancer cell labeling was achieved, and simultaneously, the Cit molecular effect on the suppression of the cancer cell line growth was investigated. As a result, the luminescence enhancement with the hybridization was successfully elucidated. In particular, the low symmetry of the coordination structure for the Eu3+ ion at the Ca(I) site provided the enhanced luminescence efficiency. Furthermore, the folate N-hydroxysuccinimidyl ester (FA-NHS) was immobilized on the Cit/Eu:HA NPs to enhance the uptake efficiency of the NPs into the cancer cells. Then, the cytocompatibility and the cell-labeling property were evaluated to investigate the effect of the NPs on the cancer cell growth suppression by the Cit molecules. Cancer cell growth suppression was successfully achieved by the interactions with the Cit/Eu:HA NPs. Furthermore, the Cit/Eu:HA NPs reacted with the cells to exhibit red-color luminescence from the cells while suppressing cancer cell growth, indicating the bifunction of cell-labeling and cytostatic suppression in one particle. The hybridized Cit molecules could significantly contribute to the tumorized cell (sphere) growth suppression. In particular, the Cit/Eu:HA NPs were effectively reacted with the spheres after a culture time of 60 h, and the luminescent labeling with following the cellular shapes could be achieved 1 h after NP addition, indicating the rapid labeling process with cytostatic suppression for interacting with the spheres.

Original languageEnglish
Pages (from-to)241-256
Number of pages16
JournalACS Applied Nano Materials
Issue number1
Publication statusPublished - Jan 24 2020
Externally publishedYes


  • bioimaging particles
  • cancer cell imaging
  • cytostatic suppression
  • hydroxyapatite nanoparticles
  • inorganic-organic nanohybrid systems
  • luminescent nanoparticles
  • photofunctional interfaces

ASJC Scopus subject areas

  • Materials Science(all)


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