Skip to main content

Advertisement

SpringerLink
Log in

Hydroxyapatite nanocrystals dually doped with fluorescent and paramagnetic labels for bimodal (luminomagnetic) cell imaging

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

Hydroxyapatite nanocrystals (HAp NCs) were prepared that contain both a fluorescent label (fluorescein) and the paramagnetic label Ho3+ ion. Synthesis was performed by a surfactant-free aqueous method using commonly available precursors and dopants. The resulting HAp NCs display a spindle like hexagonal phase morphology. Their average diameter and length are 10 and 60 nm, respectively. The photoluminescence of the HAp NCs displays substantial variation with concentration of the fluorophore. The co-dopant Ho3+ endows the nanocrystals with paramagnetism and has little effect on the luminescence of the fluorescent label. The surface of the nanocrystals was coated with polyethyleneimine and the resulting particles were covalently conjugated to folic acid in order to enable targeting of the folate receptor that is over expressed in cancer cells. The HAp NCs are biocompatible as proven by an MTT assay that revealed no apparent toxicity in doses as high as 800 μg∙mL−1 after a 48 h incubation period. The HAp NCs were used as a fluorescent bioimaging probe for in vitro imaging of HeLa cells. The characterization of the magnetic properties indicates the paramagnetic nature of the nanocrystals with a magnetization of 7.3118 emu∙g−1, and this property makes the system potentially suited for application as a Ho3+ based contrast agent for T2 magnetic resonance imaging.

Hydroxyapatite nanocrystals with fluorescent and paramagnetic labels were synthesized and characterized. The luminomagnetic nanocrystals were conjugated to folic acid and used for in vitro imaging of HeLa cells. Its biocompatibility and magnetic properties make the system a useful MRI contrast agent

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Scheme 1
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

References

  1. Hui J, Wang X (2014) Hydroxyapatite nanocrystals: colloidal chemistry, assembly and their biological applications. Inorg Chem Front 1:215–225

    Article  CAS  Google Scholar 

  2. Palmer LC, Newcomb CJ, Kaltz SR, Spoerke ED, Stupp SI (2008) Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev 108:4754–4783

    Article  CAS  Google Scholar 

  3. Liu Z, Wang Q, Yao S, Yang L, Yu S, Feng X, Li F (2014) Synthesis and characterization of Tb3+/Gd3+ dual-doped multifunctional hydroxyapatite nanoparticles. Ceram Int 40:2613–2617

    Article  CAS  Google Scholar 

  4. Chen F, Huang P, Zhu Y-J, Wu J, Zhang C-L, Cui D-X (2011) The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+/Gd3+ dual-doped hydroxyapatite nanorods. Biomaterials 32:9031–9039

    Article  CAS  Google Scholar 

  5. Chen F, Huang P, Zhu Y-J, Wu J, Cui D-X (2012) Multifunctional Eu3+/Gd3+ dual-doped calcium phosphate vesicle-like nanospheres for sustained drug release and imaging. Biomaterials 33:6447–6455

    Article  CAS  Google Scholar 

  6. Ashokan A, Menon D, Nair S, Koyakutty M (2010) A molecular receptor targeted, hydroxyapatite nanocrystals based multi-modal contrast agent. Biomaterials 31:2606–2616

    Article  CAS  Google Scholar 

  7. Unni PR, Chaudhari PR, Venkatesh M, Ramamoorthy N, Pillai MRA (2002) Preparation and bioevaluation of 166Ho labelled hydroxyapatite (HA) particles for radiosynovectomy. Nucl Med Biol 29:199–209

    Article  CAS  Google Scholar 

  8. Mader HS, Kele P, Saleh SM, Wolfbeis OS (2010) Upconverting luminescent nanoparticles for use in bioconjugation and bioimaging. Curr Opin Chem Biol 14:582–596

    Article  CAS  Google Scholar 

  9. DaCosta MV, Doughan S, Han Y, Krull UJ (2014) Lanthanide upconversion nanoparticles and applications in bioassays and bioimaging: a review. Anal Chim Acta 832:1–33

    Article  CAS  Google Scholar 

  10. Yu X, Liang S, Sun Z, Duan Y, Qin Y, Duan L, Xia H, Zhao P, Li D (2014) Microstructure and upconversion luminescence in Ho3+ and Yb3+ co-doped ZnO nanocrystalline powders. Opt Commun 313:90–93

    Article  CAS  Google Scholar 

  11. Antic Z, Lojpur V, Nikolic MG, Dordevic V, Ahrenkiel PS, Dramicanin MD (2014) Strong emission via up-conversion of Gd2O3:Yb3+, Ho3+ nanopowders co-doped with alkali metals ions. J Lumin 145:466–472

    Article  CAS  Google Scholar 

  12. Yang Y (2014) Upconversion nanophosphors for use in bioimaging, therapy, drug delivery and bioassays. Microchim Acta 181:263–294

    Article  CAS  Google Scholar 

  13. Werts MHV (2011) Near-infrared luminescent labels and probes based on lanthanide ions and their potential for applications in bioanalytical detection and imaging. In: Haenninen P, Haerma H (eds) Lanthanide luminescence: photophysical, analytical and biological aspects, springer series on fluorescence, vol 7. Springer, Heidelberg, pp 142–143

    Google Scholar 

  14. Moore EG, Szigethy G, Xu J, Palsson LO, Beeby A, Raymond KN (2008) 3-Hydroxypyridin-2-one complexes of near-infrared (NIR) emitting lanthanides: sensitization of holmium(III) and praseodymium(III) in aqueous solution. Angew Chem Int Ed 47:9500–9503

    Article  CAS  Google Scholar 

  15. Zhang J, Badger PD, Geib SJ, Petoud S (2005) Sensitization of near -infrared-emitting lanthanide cations in solution by tropolonate ligands. Angew Chem Int Ed 44:2508–2512

    Article  CAS  Google Scholar 

  16. Dosev V, Nichkova M, Kennedey IM (2008) Inorganic lanthanide nanophosphors in biotechnology. J Nanosci Nanotechnol 8:1052–1067

    CAS  Google Scholar 

  17. Hui J, Zhang X, Zhang Z, Wang S, Tao L, Wei Y, Wang X (2012) Fluoridated Hap : Ln3+ (Ln = Eu or Tb) nanoparticles for cell imaging. Nanoscale 4:6967–6970

    Article  CAS  Google Scholar 

  18. Zhang X, Hui J, Yang B, Yang Y, Fan D, Liu M, Tao L, Wei Y (2013) PEGylation of fluoridated hydroxyapatite (FAp): Ln3+ nanorods for cell imaging. Polym Chem 4:4120–4125

    Article  CAS  Google Scholar 

  19. Li X, Zeng H, Teng L, Chen H (2014) Comparative investigation on the crystal structure and cell behaviour of rare-earth doped fluorescent apatite nanocrystals. Mater Lett 125:78–81

    Article  CAS  Google Scholar 

  20. Altinoglu EI, Russin TJ, Kaiser JM, Barth BM, Eklund PC, Kester M, Adair JH (2008) Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. ACS Nano 2:2075–2084

    Article  CAS  Google Scholar 

  21. Tabakovic A, Kester M, Adair JH (2012) Calcium phosphate- based composite nanoparticles in bioimaging and therapeutic delivery applications. WIREs Nanomed Nanobiotechnol 4:96–112

    Article  CAS  Google Scholar 

  22. Imhof A, Megens M, Engelberts JJ, de Lang DTN, Sprik R, Vos WL (1999) Spectroscopy of Fluorescein (FITC) dyed colloidal silica spheres. J Phys Chem B 103:1408–1415

    Article  CAS  Google Scholar 

  23. Liu H, Chen F, Xi P, Chen B, Huang L, Cheng J, Shao C, Wang J, Bai D, Zeng Z (2011) Biocompatible fluorescent hydroxyapatite: synthesis and live cell imaging applications. J Phys Chem C 115:18538–18544

    Article  CAS  Google Scholar 

  24. Ma J, Huang P, He M, Pan L, Zhou Z, Feng L, Gao G, Cui D (2012) Folic acid-conjugated LaF3:Yb, Tm @ SiO2 nanoprobes for targeting dual-modality imaging of upconversion luminescence and X-ray computed tomography. J Phys Chem B 116:14062–14070

    Article  CAS  Google Scholar 

  25. Shojai MS, Khorasani M-T, Khoshdargi ED, Jamshidi A (2013) Synthesis methods for nanosized hydroxyapatite with diverse structures. Acta Biomater 9:7591–7621

    Article  Google Scholar 

  26. Nicolay K, Strijkers G, Grull H (2013) Gd- Containing nanoparticles as MRI contrast agents. In: Merbach A et al (eds) The chemistry of contrast agents in medical magnetic resonance imaging, 2nd edn. Wiley, UK, pp 449–483

    Chapter  Google Scholar 

  27. Norek M, Peters JA (2011) MRI contrast agents based on dysprosium or holmium. Progress NMR 59:64–82

    Article  CAS  Google Scholar 

  28. Vuong QL, Doorslaer SV, Bridot JL, Argante C, Alejandro G, Hermann R, Disch S, Mattea C, Stapf S, Gossum Y (2012) Paramagnetic nanoparticles as potential MRI contrast agents: characterization, NMR relaxation, simulations and theory. Magn Reson Mater Phys 25:467–478

    Article  CAS  Google Scholar 

  29. Cao H, Zhang L, Zheng H, Wang Z (2010) Hydroxyapatite nanocrystals for biomedical application. J Phys Chem C 114:18352–18357

    Article  CAS  Google Scholar 

  30. Murakami Y, Rikimra S, Sugo K, Kawamura K, Ogawa T, Masashiro H, Okuyama T (2008) Preparation of polyethyleneimine-hydroxyapatite and its chromatographic use. J Liq Chromatogr Relat Technol 32:407–417

    Article  Google Scholar 

  31. Murakami Y, Sugo K, Hirano M, Okuyama T (2011) Surface chemical analysis and chromatographic characterization of polyethyleneimine-coated hydroxyl apatite with various amounts of polyethyleneimine. Talanta 85:1298–1303

    Article  CAS  Google Scholar 

  32. Ai J, Xu Y, Li D, Liu Z, Wang E (2012) Folic acid as delivery vehicles: targeting folate conjugated fluorescent nanoparticles to tumors imaging. Talanta 101:32–37

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Head, Department of Chemistry, University of Kerala (Kariavattom Campus), Thiruvananthapuram, Director, CSIR-NIIST (Thiruvananthapuram), Head SAIF-IIT Madras and Director, SAIF-STIC-CUSAT (Kochi) for the sophisticated characterization techniques provided for the work.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Kerala, Kariavattom Campus, Trivandrum, 695 581, Kerala, India

    Sasidharanpillai S. Syamchand & George Sony

  2. Agro Processing and Natural Products Division, CSIR-National Institute of Interdisciplinary Science and Technology (NIIST), Pappanamcode, Trivandrum, 695 019, Kerala, India

    Sulochana Priya

Authors
  1. Sasidharanpillai S. Syamchand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sulochana Priya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Sony
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Sony.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 226 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Syamchand, S.S., Priya, S. & Sony, G. Hydroxyapatite nanocrystals dually doped with fluorescent and paramagnetic labels for bimodal (luminomagnetic) cell imaging. Microchim Acta 182, 1213–1221 (2015). https://doi.org/10.1007/s00604-014-1421-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00604-014-1421-4

Keywords

Search

Navigation