Journal of Nanoparticle Research

, Volume 13, Issue 3, pp 1139–1149 | Cite as

Silica-modified Fe-doped calcium sulfide nanoparticles for in vitro and in vivo cancer hyperthermia

  • Steven Yueh-Hsiu Wu
  • Kai-Chiang Yang
  • Ching-Li Tseng
  • Jung-Chih Chen
  • Feng-Huei Lin
Research Paper


In this study, sulfide-based magnetic Fe-doped CaS nanoparticles modified with a silica layer were investigated for cancer hyperthermia. A polyvinyl pyrrolidone polymer was used as the coupling agent. The developed nanoparticles contained 11.6 wt% iron concentration, and their X-ray diffraction pattern was similar to those of CaS and Fe–CaS nanoparticles. The average particle size was approximately 47.5 nm and homogeneously dispersed in aqueous solutions. The major absorption bands of silica were observed from the FTIR spectrum. The magnetic properties and heating efficiency were also examined. The specific absorption ratio of nanoparticles at a concentration of 10 mg/mL at 37 °C in an ethanol carrier fluid was 37.92 W/g, and the nanoparticles would raise the temperature to over 45 °C within 15 min. A cytotoxicity analysis revealed that the nanoparticles had good biocompatibility, which indicated that the nanoparticles did not affect cell viability. The therapeutic effects of the nanoparticles were investigated using in vitro and animal studies. Cells seeded with nanoparticles and treated under an AC magnetic field revealed a percentage of cytotoxicity (60%) that was significantly higher from that in other groups. In the animal study, during a hyperthermia period of 15 days, tumor-bearing Balb/c mice that were subcutaneously injected with nanoparticles and exposed to an AC magnetic field manifested a reduction in tumor volume. The newly developed silica-modified Fe–CaS nanoparticles can thus be considered a promising and attractive hyperthermia thermoseed.


Calcium sulfide Iron-doped magnetic nanoparticles Hyperthermia Silica Surface modification Targeted tumor Nanomedicine 


  1. Berry CC, Wells S, Charles S, Curtis ASG (2003) Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro. Biomaterials 24:4551–4557CrossRefGoogle Scholar
  2. Drake P, Cho HJ, Shih PS, Kao CH, Lee KF, Kuo CH, Lin XZ, Lin YJ (2007) Gd-doped iron-oxide nanoparticles for tumour therapy via magnetic field hyperthermia. J Mater Chem 17:4914–4918CrossRefGoogle Scholar
  3. Fortin JP, Gazeau F, Wilhelm C (2008) Intracellular heating of living cells through Néel relaxation of magnetic nanoparticles. Eur Biophys J 37:223–228CrossRefGoogle Scholar
  4. Graf C, Vossen DLJ, Imhof A, van Blaaderen A (2003) A general method to coat colloidal particles with silica. Langmuir 19:6693–6700CrossRefGoogle Scholar
  5. Graf C, Dembski S, Hofmann A, Rühl E (2006) A general method for the controlled embedding of nanoparticles in silica colloids. Langmuir 22:5604–5610CrossRefGoogle Scholar
  6. Gref R, Domb A, Quellec P, Blunk T, Müller RH, Verbavatz JM, Langer R (1995) The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev 16:215–233CrossRefGoogle Scholar
  7. Gupta AK, Wells S (2004) Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans Nanobiosci 3:66–73CrossRefGoogle Scholar
  8. Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499CrossRefGoogle Scholar
  9. He R, You XG, Shao J, Gao F, Pan BF, Cui DX (2007) Core/shell fluorescent magnetic silica-coated composite nanoparticles for bioconjugation. Nanotechnology 18:315601CrossRefGoogle Scholar
  10. Hou CH, Hou SM, Hsueh YS, Lin J, Wu HC, Lin FH (2009) The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy. Biomaterials 30:3956–3960CrossRefGoogle Scholar
  11. Jain TK, Reddy MK, Morales MA, Leslie-Pelecky DL, Labhasetwar V (2008) Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol Pharm 5:316–327CrossRefGoogle Scholar
  12. Johannsen M, Gneveckow U, Eckelt L, Feussner A, Waldofner N, Scholz R, Deger S, Wust P, Loening SA, Jordan A (2005a) Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique. Int J Hyperth 21:637–647CrossRefGoogle Scholar
  13. Johannsen M, Thiesen B, Jordan A, Taymoorian K, Gneveckow U, Waldöfner N, Scholz R, Koch M, Lein M, Jung K, Loening SA (2005b) Magnetic fluid hyperthermia (MFH) reduces prostate cancer growth in the orthotopic Dunning R3327 rat model. Prostate 64:283–292CrossRefGoogle Scholar
  14. Jordan A, Scholz R, Wust P, Fahling H, Felix R (1999) Magnetic fluid hyperthermia (MFH): cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles. J Magn Magn Mater 201:413–419CrossRefGoogle Scholar
  15. Jordan A, Scholz R, Maier-Hauff K, van Landeghem FK, Waldoefner N, Teichgraeber U, Pinkernelle J, Bruhn H, Neumann F, Thiesen B, von Deimling A, Felix R (2006) The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol 78:7–14CrossRefGoogle Scholar
  16. Kaman O, Pollert E, Veverka P, Veverka M, Hadová E, Knízek K, Marysko M, Kaspar P, Klementová M, Grünwaldová V, Vasseur S, Epherre R, Mornet S, Goglio G, Duguet E (2009) Silica encapsulated manganese perovskite nanoparticles for magnetically induced hyperthermia without the risk of overheating. Nanotechnology 20:275610CrossRefGoogle Scholar
  17. Kim BS, Qiu JM, Wang JP, Taton TA (2005) Magnetomicelles: composite nanostructures from magnetic nanoparticles and cross-linked amphiphilic block copolymers. Nano Lett 5:1987–1991CrossRefGoogle Scholar
  18. Lai CW, Wang YH, Lai CH, Yang MJ, Chen CY, Chou PT, Chan CS, Chi Y, Chen YC, Hsiao JK (2008) Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles: a facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy. Small 4:218–224CrossRefGoogle Scholar
  19. Lu Y, Yin YD, Mayers BT, Xia YN (2002) Modifying the surface properties of superparamagnetic iron oxide nanoparticles through a sol-gel approach. Nano Lett 2:183–186CrossRefGoogle Scholar
  20. Mykhaylyk O, Antequera YS, Vlaskou D, Plank C (2007) Generation of magnetic nonviral gene transfer agents and magnetofection in vitro. Nat Protoc 2:2391–2411CrossRefGoogle Scholar
  21. Pankhurst QA, Connolly J, Jones SK, Dobson J (2003) Applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys 36:R167–R181CrossRefGoogle Scholar
  22. Pattanaik M, Bhaumik SK (2000) Adsorption behaviour of polyvinyl pyrrolidone on oxide surfaces. Mater Lett 44:352–360CrossRefGoogle Scholar
  23. Prasad NK, Rathinasamy K, Panda D, Bahadur D (2007) Mechanism of cell death induced by magnetic hyperthermia with nanoparticles of γ-MnxFe2 − xO3 synthesized by a single step process. J Mater Chem 17:5042–5051CrossRefGoogle Scholar
  24. Raming TP, Winnubst AJA, van Kats CM, Philipse AP (2002) The synthesis and magnetic properties of nanosized hematite (α-Fe2O3) particles. J Colloid Interface Sci 249:346–350CrossRefGoogle Scholar
  25. Ren CL, Li JH, Chen XG, Hu ZD, Xue DS (2007) Preparation and properties of a new multifunctional material composed of superparamagnetic core and rhodamine B doped silica shell. Nanotechnology 18:345604CrossRefGoogle Scholar
  26. Stöber W, Fink A, Bohn E (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26:62–69CrossRefGoogle Scholar
  27. Tseng HY, Lee GB, Lee CY, Shih YH, Lin XZ (2009) Localised heating of tumours utilizing injectable magnetic nanoparticles for hyperthermia cancer therapy. IET Nanobiotechnol 3:46–54CrossRefGoogle Scholar
  28. Won J, Kim M, Yi YW, Kim YH, Jung N, Kim TK (2005) A magnetic nanoprobe technology for detecting molecular interactions in live cells. Science 309:121–125CrossRefGoogle Scholar
  29. Wu HC, Wang TW, Sun JS, Wang WH, Lin FH (2007) A novel biomagnetic nanoparticle based on hydroxyapatite. Nanotechnology 16:165601CrossRefGoogle Scholar
  30. Wu SYH, Tseng CL, Lin FH (2010) A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia. J Nanopart Res 12:1173–1185CrossRefGoogle Scholar
  31. Xu XL, Friedman G, Humfeld KD, Majetich SA, Asher SA (2002) Synthesis and utilization of monodisperse superparamagnetic colloidal particles for magnetically controllable photonic crystals. Chem Mater 14:1249–1256CrossRefGoogle Scholar
  32. Yoon TJ, Kim JS, Kim BG, Yu KN, Cho MH, Lee JK (2005) Multifunctional nanoparticles possessing a “magnetic motor effect” for drug or gene delivery. Angew Chem Int Ed Engl 44:1068–1071CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Steven Yueh-Hsiu Wu
    • 1
  • Kai-Chiang Yang
    • 1
    • 2
  • Ching-Li Tseng
    • 3
  • Jung-Chih Chen
    • 1
    • 4
  • Feng-Huei Lin
    • 1
    • 3
  1. 1.Institute of Biomedical EngineeringNational Taiwan UniversityTaipeiTaiwan
  2. 2.Department of Organ Reconstruction, Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan
  3. 3.Division of Medical Engineering ResearchNational Health Research InstitutesZhunanTaiwan
  4. 4.National Science CouncilTaipeiTaiwan, ROC

Personalised recommendations