Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment

Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia.

[1]  R. Carbone,et al.  In vitro biocompatibility of a ferrimagnetic glass-ceramic for hyperthermia application. , 2017, Materials science & engineering. C, Materials for biological applications.

[2]  M. Laranjeira,et al.  Preparation and characterization of hydroxyapatite-coated iron oxide particles by spray-drying technique. , 2009, Anais da Academia Brasileira de Ciencias.

[3]  C. Serna,et al.  Preparation of Narrow Size Distribution Superparamagnetic γ-Fe2O3 Nanoparticles in a Sol−Gel Transparent SiO2 Matrix , 2002 .

[4]  R. Gilchrist,et al.  Selective Inductive Heating of Lymph Nodes , 1957, Annals of surgery.

[5]  C Alexiou,et al.  Clinical applications of magnetic drug targeting. , 2001, The Journal of surgical research.

[6]  Isabelle Raynal,et al.  Macrophage Endocytosis of Superparamagnetic Iron Oxide Nanoparticles: Mechanisms and Comparison of Ferumoxides and Ferumoxtran-10 , 2004, Investigative radiology.

[7]  P Wust,et al.  Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitro. , 1996, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[8]  P. Harikrishna Varma,et al.  Nano iron oxide–hydroxyapatite composite ceramics with enhanced radiopacity , 2010, Journal of materials science. Materials in medicine.

[9]  G. Nussbaum Physical aspects of hyperthermia , 1982 .

[10]  Ingrid Hilger,et al.  Heating potential of iron oxides for therapeutic purposes in interventional radiology. , 2002, Academic radiology.

[11]  U. Pal,et al.  Controlling size and magnetic properties of Fe 3 O 4 clusters in solvothermal process , 2014 .

[12]  N. Turro,et al.  Spectroscopic Characterization of the Surface of Iron Oxide Nanocrystals , 2005 .

[13]  Antonio Villaverde,et al.  Biomedical applications of distally controlled magnetic nanoparticles. , 2009, Trends in biotechnology.

[14]  M. Ferraris,et al.  Synthesis of magnetic hydroxyapatite by hydrothermal–microwave technique: Dielectric, protein adsorption, blood compatibility and drug release studies , 2015 .

[15]  K. Kandori,et al.  FTIR Study on incorporation of CO2 into calcium hydroxyapatite , 1998 .

[16]  C. Li,et al.  Magnetic nanocomposite of hydroxyapatite ultrathin nanosheets/Fe3O4 nanoparticles: microwave-assisted rapid synthesis and application in pH-responsive drug release. , 2013, Biomaterials science.

[17]  A. Dey,et al.  Natural origin hydroxyapatite scaffold as potential bone tissue engineering substitute , 2016 .

[18]  Ereath Beeran Ansar,et al.  Synthesis and Characterization of Iron Oxide Embedded Hydroxyapatite Bioceramics , 2012 .

[19]  J. Kalbfleisch,et al.  Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia. , 1991, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[20]  M. Marcacci,et al.  Magnetic hydroxyapatite coatings as a new tool in medicine: A scanning probe investigation. , 2016, Materials science & engineering. C, Materials for biological applications.

[21]  S. Mondal,et al.  Processing of natural resourced hydroxyapatite ceramics from fish scale , 2010 .

[22]  V. Torchilin,et al.  Drug targeting. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[23]  Florence Gazeau,et al.  Magnetic hyperthermia efficiency in the cellular environment for different nanoparticle designs. , 2014, Biomaterials.

[24]  L. Li,et al.  Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell , 2014, Scientific Reports.

[25]  Shuhong Yu,et al.  Magnetic hydroxyapatite nanoworms for magnetic resonance diagnosis of acute hepatic injury. , 2016, Nanoscale.

[26]  W Andrä,et al.  Electromagnetic heating of breast tumors in interventional radiology: in vitro and in vivo studies in human cadavers and mice. , 2001, Radiology.

[27]  Apurba Dey,et al.  Studies on Processing and Characterization of Hydroxyapatite Biomaterials from Different Bio Wastes , 2012 .

[28]  N. M. Sundaram,et al.  Preparation and characterization of an iron oxide-hydroxyapatite nanocomposite for potential bone cancer therapy , 2015, International journal of nanomedicine.

[29]  Tzu-Wei Wang,et al.  A novel biomagnetic nanoparticle based on hydroxyapatite , 2007 .

[30]  L. Kavitha,et al.  Synthesis and spectroscopic characterization of magnetic hydroxyapatite nanocomposite using ultrasonic irradiation. , 2012, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[31]  F. Lin,et al.  The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy. , 2009, Biomaterials.

[32]  H. Kim,et al.  A novel preparation of magnetic hydroxyapatite nanotubes , 2012 .

[33]  S. Kalkura,et al.  Physicochemical and biological properties of iron and zinc ions co-doped nanocrystalline hydroxyapatite, synthesized by ultrasonication , 2014 .

[34]  D. Mangalaraj,et al.  Facile in situ growth of Fe3O4 nanoparticles on hydroxyapatite nanorods for pH dependent adsorption and controlled release of proteins , 2014 .

[35]  Junghwan Oh,et al.  Magnetic hyperthermia and pH-responsive effective drug delivery to the sub-cellular level of human breast cancer cells by modified CoFe2O4 nanoparticles. , 2017, Biochimie.

[36]  T. Webster,et al.  Increased osteoblast functions in the presence of hydroxyapatite-coated iron oxide nanoparticles. , 2011, Acta biomaterialia.

[37]  Thi Tuong Vy Phan,et al.  Synthesis of amine-polyglycidol functionalised Fe3O4@SiO2 nanocomposites for magnetic hyperthermia, pH-responsive drug delivery, and bioimaging applications , 2016 .

[38]  W. Rogers,et al.  Factors regulating macrophage endocytosis of nanoparticles: implications for targeted magnetic resonance plaque imaging. , 2005, Atherosclerosis.

[39]  B. Jeyadevan,et al.  Hydrothermal synthesis of magnetite/hydroxyapatite composite material for hyperthermia therapy for bone cancer , 2008 .

[40]  P. Decuzzi,et al.  Assembly of Iron Oxide Nanocubes for Enhanced Cancer Hyperthermia and Magnetic Resonance Imaging , 2017, Nanomaterials.

[41]  N. Sokolova,et al.  Calcium Hydroxyapatite for Medical Applications , 2004 .

[42]  E. Landi,et al.  Intrinsic magnetism and hyperthermia in bioactive Fe-doped hydroxyapatite. , 2012, Acta biomaterialia.