Pharmaceutical Research

, Volume 29, Issue 5, pp 1180–1188 | Cite as

Magnetic Nanoparticles for Cancer Diagnosis and Therapy

  • Mehmet V. Yigit
  • Anna Moore
  • Zdravka Medarova
Expert review


Nanotechnology is evolving as a new field that has a potentially high research and clinical impact. Medicine, in particular, could benefit from nanotechnology, due to emerging applications for noninvasive imaging and therapy. One important nanotechnological platform that has shown promise includes the so-called iron oxide nanoparticles. With specific relevance to cancer therapy, iron oxide nanoparticle-based therapy represents an important alternative to conventional chemotherapy, radiation, or surgery. Iron oxide nanoparticles are usually composed of three main components: an iron core, a polymer coating, and functional moieties. The biodegradable iron core can be designed to be superparamagnetic. This is particularly important, if the nanoparticles are to be used as a contrast agent for noninvasive magnetic resonance imaging (MRI). Surrounding the iron core is generally a polymer coating, which not only serves as a protective layer but also is a very important component for transforming nanoparticles into biomedical nanotools for in vivo applications. Finally, different moieties attached to the coating serve as targeting macromolecules, therapeutics payloads, or additional imaging tags. Despite the development of several nanoparticles for biomedical applications, we believe that iron oxide nanoparticles are still the most promising platform that can transform nanotechnology into a conventional medical discipline.


cancer diagnosis drug delivery gene delivery iron oxide nanoparticle magnetic nanoparticle  molecular imaging MRI nanomedicine siRNA therapy  



antigen-presenting cell


drug-delivering magnetic nanoparticles






green fluorescent protein


anti HER2/neu antibody


irrelevant antibody


magnetic nanoparticle


near infrared


red fluorescent protein


transverse relaxation rate


longitudinal relaxation time


transverse relaxation time


  1. 1.
    Pautler M, Brenner S. Nanomedicine: promises and challenges for the future of public health. Int J Nanomedicine. 2010;5:803–9.PubMedGoogle Scholar
  2. 2.
    Kievit FM, Zhang M. Surface engineering of iron oxide nanoparticles for targeted cancer therapy. Acc Chem Res 2011;44:853–62.Google Scholar
  3. 3.
    Gupta AK, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans NanoBiosci. 2004;3:66–73.CrossRefGoogle Scholar
  4. 4.
    Pankhurst QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. J Phys D: Appl Phys. 2003;36:R167–81.CrossRefGoogle Scholar
  5. 5.
    Anzai Y, Piccoli CW, Outwater EK, et al. Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study. Radiology. 2003;228:777–88.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim HS, Oh SY, Joo HJ, Son KR, Song IC, Moon WK. The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells. NMR Biomed. 2010;23:514–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Provenzano R, Schiller B, Rao M, Coyne D, Brenner L, Pereira BJG. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2009;4:386–93.PubMedCrossRefGoogle Scholar
  8. 8.
    Saokar A, Gee MS, Islam T, Mueller PR, Harisinghani MG. Appearance of primary lymphoid malignancies on lymphotropic nanoparticle-enhanced magnetic resonance imaging using ferumoxtran-10. Clin Imag. 2010;34:448–52.CrossRefGoogle Scholar
  9. 9.
    Spinowitz BS, Kausz AT, Baptista J, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008;19:1599–605.PubMedCrossRefGoogle Scholar
  10. 10.
    Babes L, Denizot B, Tanguy G, Le JJJ, Jallet P. Synthesis of iron oxide nanoparticles used as MRI contrast agents: a parametric study. J Colloid Interface Sci. 1999;212:474–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 2004;17:484–99.PubMedCrossRefGoogle Scholar
  12. 12.
    Sjogren CE, Briley-Saebo K, Hanson M, Johansson C. Magnetic characterization of iron oxides for magnetic resonance imaging. Magn Reson Med. 1994;31:268–72.PubMedCrossRefGoogle Scholar
  13. 13.
    Weissleder R, Bogdanov A, Neuwelt EA, Papisov M. Long-circulating iron oxides for MR imaging. Adv Drug Delivery Rev. 1995;16:321–33.CrossRefGoogle Scholar
  14. 14.
    Josephson L, Lewis J, Jacobs P, Hahn PF, Stark DD. The effects of iron oxides on proton relaxivity. Magn Reson Imag. 1988;6:647–53.CrossRefGoogle Scholar
  15. 15.
    Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2005;26:3995–4021.PubMedCrossRefGoogle Scholar
  16. 16.
    Sun C, Du K, Fang C, et al. PEG-Mediated synthesis of highly dispersive multifunctional superparamagnetic nanoparticles: their physicochemical properties and function in vivo. ACS Nano. 2010;4:2402–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhang Y, Kohler N, Zhang M. Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials. 2002;23:1553–61.PubMedCrossRefGoogle Scholar
  18. 18.
    Corsi F, De Palma C, Colombo M, et al. Towards ideal magnetofluorescent nanoparticles for bimodal detection of breast-cancer cells. Small. 2009;5:2555–64.PubMedCrossRefGoogle Scholar
  19. 19.
    Pittet MJ, Swirski FK, Reynolds F, Josephson L, Weissleder R. Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles. Nat Protoc. 2006;1:73–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang P, Yigit MV, Medarova Z, et al. Combined small interfering RNA therapy and in vivo magnetic resonance imaging in islet transplantation. Diabetes. 2011;60:565–71.PubMedCrossRefGoogle Scholar
  21. 21.
    Bae KH, Kim YB, Lee Y, Hwang J, Park H, Park TG. Bioinspired synthesis and characterization of gadolinium-labeled magnetite nanoparticles for dual contrast T1- and T2-weighted magnetic resonance imaging. Bioconjugate Chem. 2010;21:505–12.CrossRefGoogle Scholar
  22. 22.
    Yang X, Hong H, Grailer JJ, et al. cRGD-functionalized, DOX-conjugated, and Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials. 2011;32:4151–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Yigit MV, Zhu L, Ifediba MA, et al. Noninvasive MRI-SERS imaging in living mice using an innately bimodal nanomaterial. ACS Nano. 2011;5:1056–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen FH, Zhang LM, Chen QT, Zhang Y, Zhang ZJ. Synthesis of a novel magnetic drug delivery system composed of doxorubicin-conjugated Fe3O4 nanoparticle cores and a PEG-functionalized porous silica shell. Chem Commun (Camb). 2010;46:8633–5.CrossRefGoogle Scholar
  25. 25.
    Gaihre B, Khil MS, Kim HY. In vitro anticancer activity of doxorubicin-loaded gelatin-coated magnetic iron oxide nanoparticles. J Microencapsul. 2011;28:286–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Kievit FM, Wang FY, Fang C, et al. Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro. J Contr Release. 2011;152:76–83.CrossRefGoogle Scholar
  27. 27.
    Lee JH, Lee K, Moon SH, Lee Y, Park TG, Cheon J. All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular imaging and siRNA delivery. Angew Chem Int Ed. 2009;48:4174–9.CrossRefGoogle Scholar
  28. 28.
    Taratula O, Garbuzenko O, Savla R, Wang YA, He H, Minko T. Multifunctional nanomedicine platform for cancer specific delivery of siRNA by superparamagnetic iron oxide nanoparticles-dendrimer complexes. Curr Drug Deliv. 2011;8:59–69.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang H, Lee MY, Hogg MG, Dordick JS, Sharfstein ST. Gene delivery in three-dimensional cell cultures by superparamagnetic nanoparticles. ACS Nano. 2010;4:4733–43.PubMedCrossRefGoogle Scholar
  30. 30.
    Ellerby HM, Arap W, Ellerby LM, et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999;5:1032–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Lee CS, Lee H, Westervelt RM. Microelectromagnets for the control of magnetic nanoparticles. Appl Phys Lett. 2001;79:3308–10.CrossRefGoogle Scholar
  32. 32.
    Stolnik S, Illum L, Davis SS. Long circulating microparticulate drug carriers. Adv Drug Deliv Rev. 1995;16:195–214.CrossRefGoogle Scholar
  33. 33.
    Gupta AK, Curtis ASG. Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors. Biomaterials. 2004;25:3029–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Tourinho F, Franck R, Massart R, Perzynski R. Synthesis and magnetic properties of manganese and cobalt ferrite ferrofluids. Prog Colloid Polym Sci. 1989;79:128–34.CrossRefGoogle Scholar
  35. 35.
    Kim DK, Zhang Y, Voit W, Rao KV, Muhammed M. Synthesis and characterization of surfactant-coated superparamagnetic monodispersed iron oxide nanoparticles. J Magn Magn Mater. 2001;225:30–6.CrossRefGoogle Scholar
  36. 36.
    Portet D, Denizot B, Rump E, Lejeune J-J, Jallet P. Nonpolymeric coatings of iron oxide colloids for biological use as magnetic resonance imaging contrast agents. J Colloid Interface Sci. 2001;238:37–42.PubMedCrossRefGoogle Scholar
  37. 37.
    Bonnemain B. Superparamagnetic agents in magnetic resonance imaging. Physicochemical characteristics and clinical applications. A review. J Drug Target. 1998;6:167–74.PubMedCrossRefGoogle Scholar
  38. 38.
    Kim DK, Zhang Y, Voit W, et al. Superparamagnetic iron oxide nanoparticles for bio-medical applications. Scr Mater. 2001;44:1713–7.CrossRefGoogle Scholar
  39. 39.
    Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11:2319–31.PubMedCrossRefGoogle Scholar
  40. 40.
    Bean CP, Livingston JD. Superparamagnetism. J Appl Phys. 1959;30:120S–9S.CrossRefGoogle Scholar
  41. 41.
    Tartaj P, Morales MdP, Veintemillas-Verdaguer S, Gonzalez-Carreno T, Serna CJ. The preparation of magnetic nanoparticles for applications in biomedicine. J Phys D: Appl Phys. 2003;36:R182–97.CrossRefGoogle Scholar
  42. 42.
    Goya GF, Berquó TS, Fonseca FC, Morales MP. Static and dynamic magnetic properties of spherical magnetite nanoparticles. J Appl Phys. 2003;94:3520–8.CrossRefGoogle Scholar
  43. 43.
    Jeong U, Teng X, Wang Y, Yang H, Xia Y. Superparamagnetic colloids: controlled synthesis and niche applications. Adv Mater. 2007;19:33–60.CrossRefGoogle Scholar
  44. 44.
    Mikhaylova M, Kim DK, Bobrysheva N, et al. Superparamagnetism of magnetite nanoparticles: dependence on surface modification. Langmuir. 2004;20:2472–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Bedanta S, Kleemann W. Supermagnetism. J Phys D: Appl Phys 2009;42 013001.Google Scholar
  46. 46.
    Kumar M, Yigit M, Dai G, Moore A, Medarova Z. Image-guided breast tumor therapy using a small interfering RNA nanodrug. Cancer Res. 2010;70:7553–61.PubMedCrossRefGoogle Scholar
  47. 47.
    Medarova Z, Pham W, Farrar C, Petkova V, Moore A. In-vivo imaging of siRNA delivery and silencing in tumors. Nat Med. 2007;13:372–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Medarova Z, Rashkovetsky L, Pantazopoulos P, Moore A. Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging. Cancer Res. 2009;69:1182–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Sun C, Lee JS, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev. 2008;60:1252–65.PubMedCrossRefGoogle Scholar
  50. 50.
    Ferrari M. Vectoring siRNA therapeutics into the clinic. Nat Rev Clin Oncol. 2010;7:485–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci U S A. 2007;104:15549–54.PubMedCrossRefGoogle Scholar
  52. 52.
    Kievit FM, Veiseh O, Fang C, et al. Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. ACS Nano. 2010;4:4587–94.PubMedCrossRefGoogle Scholar
  53. 53.
    Mikhaylova M, Stasinopoulos I, Kato Y, Artemov D, Bhujwalla ZM. Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA. Cancer Gene Ther. 2009;16:217–26.PubMedGoogle Scholar
  54. 54.
    Agrawal A, Min DH, Singh N, et al. Functional delivery of siRNA in mice using dendriworms. ACS Nano. 2009;3:2495–504.PubMedCrossRefGoogle Scholar
  55. 55.
    Yang J, Lee CH, Ko HJ, et al. Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer. Angew Chem Int Ed Engl. 2007;46:8836–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Yu MK, Jeong YY, Park J, et al. Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew Chem Int Ed Engl. 2008;47:5362–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Lim E-K, Huh Y-M, Yang J, Lee K, Suh J-S, Haam S. pH-Triggered drug-releasing magnetic nanoparticles for cancer therapy guided by molecular imaging by MRI. Adv Mater. 2011;23:2436–42.PubMedCrossRefGoogle Scholar
  58. 58.
    Yu MK, Kim D, Lee I-H, So J-S, Jeong YY, Jon S. Image-guided prostate cancer therapy using aptamer-functionalized thermally cross-linked superparamagnetic iron oxide nanoparticles. Small. 2011;7:2241–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Srinivas M, Aarntzen EH, Bulte JW, et al. Imaging of cellular therapies. Adv Drug Deliv Rev. 2010;62:1080–93.PubMedCrossRefGoogle Scholar
  60. 60.
    Roach 3rd M, Alberini JL, Pecking AP, et al. Diagnostic and therapeutic imaging for cancer: therapeutic considerations and future directions. J Surg Oncol. 2011;103:587–601.PubMedCrossRefGoogle Scholar
  61. 61.
    Spencer SS, Theodore WH, Berkovic SF. Clinical applications: MRI, SPECT, and PET. Magn Reson Imag. 1995;13:1119–24.CrossRefGoogle Scholar
  62. 62.
    de Vries IJ, Lesterhuis WJ, Barentsz JO, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 2005;23:1407–13.PubMedCrossRefGoogle Scholar
  63. 63.
    Long CM, van Laarhoven HW, Bulte JW, Levitsky HI. Magnetovaccination as a novel method to assess and quantify dendritic cell tumor antigen capture and delivery to lymph nodes. Cancer Res. 2009;69:3180–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Singh N, Jenkins GJ, Asadi R, Doak SH. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev 2010;1:5358. doi: 10.3402/nano.v1i0.5358.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mehmet V. Yigit
    • 1
  • Anna Moore
    • 1
  • Zdravka Medarova
    • 1
  1. 1.Department of Radiology, Molecular Imaging LaboratoryAthinoula A. Martinos Center for Biomedical ImagingMassachusetts General Hospital Harvard Medical SchoolCharlestownUSA

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