Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as Multifunctional Cancer Theranostics

  • Ibrahim M. El-SherbinyEmail author
  • Mousa El-Sayed
  • Asmaa Reda
Part of the Nanomedicine and Nanotoxicology book series (NANOMED)


Nanobiotechnology stemmed from the recruitment of tools developed by nanotechnology to be applied in many other sectors, including nanomedicine. Particularly, magnetic nanoparticles (MNPs) are of great interest, having successfully offered controlled sizes, capability to be manipulated externally, localized magnetic hyperthermia treatment (MHT), and enhanced magnetic resonance imaging (MRI). As a result, these MNPs are used as therapeutic and diagnostic tools in a variety of biomedical applications such as cancer, Alzheimer, and bacterial infections. In this regard, novel insights provide rationale for designing and development of superparamagnetic iron oxide nanoparticles (SPIONs) to be utilized in various biomedical applications, especially given that SPIONs are already used in clinical trials in late phases. These magic nanoparticles opened avenues to drug delivery, cellular-specific targeting, multi-modal imaging, and a new era of personalized medicine for management of cancer. Herein, we will unravel the extra-unique properties of SPIONs endowing the multifunctional characteristics and abilities for diagnosis, therapy, and online therapeutic monitoring that are referred to theranostics. Moreover, huge efforts have been exerted recently on designing and developing of SPIONs with enhanced biocompatibility, safety, drug-loading capacity, stability, and imaging ability. In addition, the minimization of cellular uptake by macrophages, preferential targeting of cancerous cells sparing normal cells, monitoring cancer cells prior to and after treatment, as well as triggering therapeutic drug release in a controlled fashion envisioned SPION as a golden therapeutic era tool. Overall, this book chapter will highlight the state-of-the-art designed SPIONs, their fabrication, characterization, and the mechanism of their action in targeting cancer cells.


SPIONs Cancer Theranostics Drug delivery Diagnosis Magnetic Nanoparticles 


  1. Allard-Vannier E et al (2012) Pegylated magnetic nanocarriers for doxorubicin delivery: a quantitative determination of stealthiness in vitro and in vivo. Eur J Pharm Biopharm: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.81: 498–505.
  2. Alwi R et al (2012) Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics. Biomed Opt Express 3:2500–2509. Scholar
  3. Ashokkumar M, Lee J, Kentish S, Grieser F (2007) Bubbles in an acoustic field: an overview. Ultrason Sonochemistry 14:470–475. Scholar
  4. Bannerman AD, Li X, Wan W (2017) A ‘degradable’ poly (vinyl alcohol) iron oxide nanoparticle hydrogel. Acta Biomater 58:376–385. Scholar
  5. Bano S et al (2016) Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, T 2 relaxometry, and photodynamic treatment potential. Int J Nanomedicine 11:3833–3848. Scholar
  6. Bee A, Massart R, Neveu S (1995) Synthesis of very fine maghemite particles. J Magn Magn Mater, pp 6–9.
  7. Bellova A et al (2010) Effect of Fe3O4 magnetic nanoparticles on lysozyme amyloid aggregation. Nanotechnology 21:065103. Scholar
  8. Cen C et al (2019) Improving magnetofection of magnetic polyethylenimine nanoparticles into MG-63 osteoblasts using a novel uniform magnetic field. Nanoscale research letters 14(90).
  9. Chen B, Wu W, Wang X (2011) Magnetic iron oxide nanoparticles for tumor-targeted therapy. Curr Cancer Drug Targets 11:184–189CrossRefGoogle Scholar
  10. Cheng FY et al (2005) Characterization of aqueous dispersions of Fe3O4 nanoparticles and their biomedical applications. Biomaterials 26:729–738. Scholar
  11. Cheng KK et al (2015) Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI). Biomaterials 44:155–172. Scholar
  12. Corot C, Robert P, Idee JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504. Scholar
  13. Dilnawaz F, Singh A, Mohanty C, Sahoo SK (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31:3694–3706. Scholar
  14. Ding Z et al (2017) Redox-responsive dextran based theranostic nanoparticles for near-infrared/magnetic resonance imaging and magnetically targeted photodynamic therapy. Biomater Sci 5:762–771. Scholar
  15. Dolores R, Raquel S, Adianez GL (2015) Sonochemical synthesis of iron oxide nanoparticles loaded with folate and cisplatin: effect of ultrasonic frequency. Ultrason Sonochemistry 23:391–398. Scholar
  16. Du SW et al (2018) Combined phycocyanin and hematoporphyrin monomethyl ether for breast cancer treatment via photosensitizers modified Fe3O4 nanoparticles inhibiting the proliferation and migration of MCF-7 cells. Biomacromol 19:31–41. Scholar
  17. Durdureanu-Angheluta A et al (2010) Synthesis and characterization of magnetite particles covered with a-trietoxysilil-polydimethylsiloxane. J Magn Magn Mater 322:2956–2968. Scholar
  18. Eyvazzadeh N et al (2017) Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer. Lasers Med Sci 32:1469–1477. Scholar
  19. Frullano L, Meade TJ (2007) Multimodal MRI contrast agents. J Biol Inorg Chem JBIC Publ Soc Biol Inorg Chem 12:939–949. Scholar
  20. Fu G et al (2014) Magnetic prussian blue nanoparticles for targeted photothermal therapy under magnetic resonance imaging guidance. Bioconjugate chemistry 25:1655–1663. Scholar
  21. Ghaznavi H et al (2018) Folic acid conjugated PEG coated gold-iron oxide core-shell nanocomplex as a potential agent for targeted photothermal therapy of cancer. Artif Cells Nanomedicine, Biotechnol 46:1594–1604. Scholar
  22. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRefGoogle Scholar
  23. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. Scholar
  24. Hoang MD et al. (2015) Branched polyethylenimine-superparamagnetic iron oxide nanoparticles (bPEI-SPIONs) improve the immunogenicity of tumor antigens and enhance Th1 polarization of dendritic cells. Journal of immunology research 2015, 706379.
  25. Hong S (2010) Chitosan-coated ferrite (Fe3O4) nanoparticles as a T2 contrast agent for magnetic resonance imaging. J Korean Phys Soc 56:868–873CrossRefGoogle Scholar
  26. Huang YF, Wang YF, Yan XP (2010) Amine-functionalized magnetic nanoparticles for rapid capture and removal of bacterial pathogens. Environmental science & technology 44:7908–7913. Scholar
  27. Huang G et al (2013) Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy. Theranostics 3:116–126. Scholar
  28. Huang KS, Shieh DB, Yeh CS, Wu PC, Cheng FY (2014) Antimicrobial applications of water-dispersible magnetic nanoparticles in biomedicine. Current medicinal chemistry 21:3312–3322CrossRefGoogle Scholar
  29. Ishikawa T, Kataoka S, Kandori K (1993) The influence of carboxylate ions on the growth of p-FeOOH particles. J Mater Sci 28:2693–2698. Scholar
  30. Jallouk AP, Palekar RU, Pan H, Schlesinger PH, Wickline SA (2015) Modifications of natural peptides for nanoparticle and drug design. Adv Protein Chem Struct Biol 98:57–91. Scholar
  31. Kang SH, Hong SP, Kang BS (2018) Targeting chemo-proton therapy on C6 cell line using superparamagnetic iron oxide nanoparticles conjugated with folate and paclitaxel. Int J Radiat Biol 94:1006–1016. Scholar
  32. Kijima N, Yoshinag M, Awaka J, Akimoto J (2011) Microwave synthesis, characterization, and electrochemical properties of α-Fe2O3 nanoparticles. Solid State Ions 192: 293–297.
  33. Kim KS et al (2016) Correction: stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy. Nanoscale 8:12843. Scholar
  34. Kim MC et al (2017) Polyethyleneimine-associated polycaprolactone-Superparamagnetic iron oxide nanoparticles as a gene delivery vector. J Biomed Mater Res Part B Appl Biomater 105:145–154. Scholar
  35. Korpany KV et al (2016) One-step ligand exchange and switching from hydrophobic to water-stable hydrophilic superparamagnetic iron oxide nanoparticles by mechanochemical milling. Chem Commun 52:3054–3057. Scholar
  36. Krol S et al (2013) Therapeutic benefits from nanoparticles: the potential significance of nanoscience in diseases with compromise to the blood brain barrier. Chem Rev 113:1877–1903. Scholar
  37. Kruijshaar ME et al (2008) Increasing antituberculosis drug resistance in the United Kingdom: analysis of national surveillance data. BMJ 336:1231–1234. Scholar
  38. Lam T et al (2016) Fabricating water dispersible superparamagnetic iron oxide nanoparticles for biomedical applications through ligand exchange and direct conjugation. Nanomaterials 6.
  39. Lee J, Isobe T, Senna M (1996) Magnetic properties of ultrafine magnetite particles and their slurries prepared via in-situ precipitation. Colloids SurfS A PhysChemical Eng Asp 109:121–127. Scholar
  40. Liu B, Liu ZL, Li XW (2004) Synthesis of magnetite nanoparticles in W/O microemulsion. J Mater Sci 39:2633–2636. Scholar
  41. Maity D, Ding J, Xue JM (2008) Synthesis of magnetite nanoparticles by thermal decomposition: time, temperature, surfactant and solvent effects. Funct Mater Lett 1:189–193. Scholar
  42. Maity D, Choo SG, Yi J, Ding J, Xue JM (2009) Synthesis of magnetite nanoparticles via a solvent-free thermal decomposition route. J Magn Magn Mater 321:1256–1259. Scholar
  43. Malekkhaiat Haffner S, Malmsten M (2017) Membrane interactions and antimicrobial effects of inorganic nanoparticles. Adv Colloid Interface Sci 248:105–128. Scholar
  44. Mitchell E et al (2014) Probing on the hydrothermally synthesized iron oxide nanoparticles for ultra-capacitor applications. Powder Technol. Scholar
  45. Mohammed L, Gomaa HG, Ragab D, Zhu J (2016) Magnetic nanoparticles for environmental and biomedical applications: a review. Particuology
  46. Morrow M, Waters J, Morris E (2011) MRI for breast cancer screening, diagnosis, and treatment. Lancet 378:1804–1811. Scholar
  47. Moura CC, Segundo MA, Neves J, Reis S, Sarmento B (2014) Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application. Int J Nanomedicine 9:4911–4922. Scholar
  48. Munita JM, Arias CA (2016) Mechanisms of antibiotic resistance. Microbiol Spectr 4.
  49. Murray CB, Noms DJ, Bawend MG (1993) Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites. J Am Chem Soc 115:8706–8715. Scholar
  50. Nadeem M et al. (2016) Magnetic properties of polyvinyl alcohol and doxorubicin loaded iron oxide nanoparticles for anticancer drug delivery applications. PloS one 11: e0158084.
  51. Nigam S, Bahadur D (2017) Dendrimer-conjugated iron oxide nanoparticles as stimuli-responsive drug carriers for thermally-activated chemotherapy of cancer. Colloids Surf B Biointerfaces 155:182–192. Scholar
  52. Niu C et al (2013) Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes. Biomaterials 34:2307–2317. Scholar
  53. O’Brien S, Brus L, Murray CB (2001) Synthesis of monodisperse nanoparticles of barium titanate: toward a generalized strategy of oxide nanoparticle synthesis. J Am Chem Soc 123:12085–12086. Scholar
  54. Ostroverkhov PV et al (2019) Synthesis and characterization of bacteriochlorin loaded magnetic nanoparticles (MNP) for personalized MRI guided photosensitizers delivery to tumor. J Colloid Interface Sci 537:132–141. Scholar
  55. Pascu Oana et al (2012) Surface reactivity of iron oxide nanoparticles by microwave assisted synthesis; comparison with the thermal decomposition route. J Phys Chem. Scholar
  56. Perez JM, Josephson L, O’Loughlin T, Hogemann D, Weissleder R (2002) Magnetic relaxation switches capable of sensing molecular interactions. Nat Biotechnol 20:816–820. Scholar
  57. Pinkas J et al (2008) Sonochemical synthesis of amorphous nanoscopic iron(III) oxide from Fe(acac)3. Ultrason Sonochemistry 15:257–264. Scholar
  58. Qin J et al (2007) A high-performance magnetic resonance imaging T2 Contrast Agent. Adv Mater 19:1874–1878. Scholar
  59. Reddy LH, Arias JL, Nicolas J, Couvreur P (2012) Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem Rev 112:5818–5878. Scholar
  60. Ren C et al (2008) Synthesis of organic dye-impregnated silica shell-coated iron oxide nanoparticles by a new method. Nanoscale Res Lett 3:496–501. Scholar
  61. Rosen JE, Chan L, Shieh DB, Gu FX (2012) Iron oxide nanoparticles for targeted cancer imaging and diagnostics. Nanomedicine 8:275–290. Scholar
  62. Salaheldin TA, Loutfy SA, Ramadan MA, Youssef T, Mousa SA (2019) IR-enhanced photothermal therapeutic effect of graphene magnetite nanocomposite on human liver cancer HepG2 cell model. Int J Nanomedicine 14:4397–4412. Scholar
  63. Shaghaghi B, Khoee S, Bonakdar S (2019) Preparation of multifunctional Janus nanoparticles on the basis of SPIONs as targeted drug delivery system. Int J Pharm 559:1–12. Scholar
  64. Shang L, Wang QY, Chen KL, Qu J, Zhou QH, Luo JB, Lin J (2017) SPIONs/DOX loaded polymer nanoparticles for MRI detection and efficient cell targeting drug delivery. RSC Advances 7.
  65. Shen S et al (2015) Core-shell structured Fe3O4@TiO2-doxorubicin nanoparticles for targeted chemo-sonodynamic therapy of cancer. Int J Pharm 486:380–388. Scholar
  66. Shi J et al (2013) PEGylated fullerene/iron oxide nanocomposites for photodynamic therapy, targeted drug delivery and MR imaging. Biomaterials 34:9666–9677. Scholar
  67. Snell NJ (2003) Examining unmet needs in infectious disease. Drug Discov Today 8, 22–30Google Scholar
  68. Sodipo BK, Aziz AA (2018) One minute synthesis of amino-silane functionalized superparamagnetic iron oxide nanoparticles by sonochemical method. Ultrason Sonochemistry 40:837–840. Scholar
  69. Solanki A, Kim JD, Lee KB (2008) Nanotechnology for regenerative medicine: nanomaterials for stem cell imaging. Nanomedicine 3:567–578. Scholar
  70. Stewart BW, W. C. World Cancer Report (2014)Google Scholar
  71. Tassa C, Shaw SY, Weissleder R (2011) Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. Acc Chem Res 44:842–852. Scholar
  72. Tong L, Zhao M, Zhu S, Chen J (2011) Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging of cancer. Front Med 5:379–387. Scholar
  73. Torres-Sangiao E, Holban AM, Gestal MC (2016) Advanced nanobiomaterials: vaccines, diagnosis and treatment of infectious diseases. Molecules 21.
  74. Turkbey B, Thomasson D, Pang Y, Bernardo M, Choyke PL (2010) The role of dynamic contrast-enhanced MRI in cancer diagnosis and treatment. Diagn Interv Radiol 16:186–192. Scholar
  75. Tutuianu R et al. (2017) Evaluation of the ability of nanostructured PEI-coated iron oxide nanoparticles to incorporate cisplatin during synthesis. Nanomaterials 7.
  76. Veiseh O, Gunn JW, Zhang M (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 62:284–304. Scholar
  77. Vetter A et al (2011) Thiolated polyacrylic acid-modified iron oxide nanoparticles for in vitro labeling and MRI of stem cells. J Drug Target 19:562–572. Scholar
  78. Vikram S et al (2015) Tuning the magnetic properties of iron oxide nanoparticles by a room-temperature air-atmosphere (RTAA) co-precipitation method. J Nanosci Nanotechnol 15:3870–3878. Scholar
  79. Wang Y et al. (2018) Multistage targeting strategy using magnetic composite nanoparticles for synergism of photothermal therapy and chemotherapy. Small 14: e1702994.
  80. Wei H et al (2017) Exceedingly small iron oxide nanoparticles as positive MRI contrast agents. Proc Natl Acad Sci USA 114:2325–2330. Scholar
  81. Xu Y, Qin Y, Palchoudhury S, Bao Y (2011) Water-soluble iron oxide nanoparticles with high stability and selective surface functionality. Langmuir ACS J Surf Colloids 27:8990–8997. Scholar
  82. Yan L et al. (2018) Protoporphyrin IX (PpIX)-coated superparamagnetic iron oxide nanoparticle (SPION) nanoclusters for magnetic resonance imaging and photodynamic therapy. Adv Funct Mater 28.
  83. Yigit MV, Moore A, Medarova Z (2012) Magnetic nanoparticles for cancer diagnosis and therapy. Pharm Res 29:1180–1188. Scholar
  84. Yu M, Huang S, Yu KJ, Clyne AM (2012) Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture. Int J Mol Sci 13:5554–5570. Scholar
  85. Zazo H, Colino CI, Lanao JM (2016) Current applications of nanoparticles in infectious diseases. J Control Release Off J Control Release Soc 224:86–102. Scholar
  86. Zhang P et al (2018) Iron oxide nanoparticles as nanocarriers to improve chlorin e6-based sonosensitivity in sonodynamic therapy. Drug Des Dev Ther 12:4207–4216. Scholar
  87. Zou P et al (2010) Superparamagnetic iron oxide nanotheranostics for targeted cancer cell imaging and pH-dependent intracellular drug release. Mol Pharm 7:1974–1984. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Ibrahim M. El-Sherbiny
    • 1
    Email author
  • Mousa El-Sayed
    • 1
  • Asmaa Reda
    • 1
    • 2
  1. 1.Center for Materials Science, Zewail City of Science and TechnologyGizaEgypt
  2. 2.Molecular and Cellular Biology Division, Zoology Department, Faculty of ScienceBenha UniversityBenhaEgypt

Personalised recommendations