Theranostic Magnetic Nanostructures (MNS) for Cancer

  • Vikas Nandwana
  • Mrinmoy De
  • Shihyao Chu
  • Manish Jaiswal
  • Matt Rotz
  • Thomas J. Meade
  • Vinayak P. Dravid

Abstract

Despite the complexities of cancer, remarkable diagnostic and therapeutic advances have been made during the past decade, which include improved genetic, molecular, and nanoscale understanding of the disease. Physical science and engineering, and nanotechnology in particular, have contributed to these developments through out-of-the-box ideas and initiatives from perspectives that are far removed from classical biological and medicinal aspects of cancer. Nanostructures, in particular, are being effectively utilized in sensing/diagnostics of cancer while nanoscale carriers are able to deliver therapeutic cargo for timed and controlled release at localized tumor sites. Magnetic nanostructures (MNS) have especially attracted considerable attention of researchers to address cancer diagnostics and therapy. A significant part of the promise of MNS lies in their potential for “theranostic” applications, wherein diagnostics makes use of the enhanced localized contrast in magnetic resonance imaging (MRI) while therapy leverages the ability of MNS to heat under external radio frequency (RF) field for thermal therapy or use of thermal activation for release of therapy cargo. In this chapter, we report some of the key developments in recent years in regard to MNS as potential theranostic carriers. We describe that the r2 relaxivity of MNS can be maximized by allowing water (proton) diffusion in the vicinity of MNS by polyethylene glycol (PEG) anchoring, which also facilitates excellent fluidic stability in various media and extended in vivo circulation while maintaining high r2 values needed for T2-weighted MRI contrast. Further, the specific absorption rate (SAR) required for thermal activation of MNS can be tailored by controlling composition and size of MNS. Together, emerging MNS show considerable promise to realize theranostic potential. We discuss that properly functionalized MNS can be designed to provide remarkable in vivo stability and accompanying pharmacokinetics exhibit organ localization that can be tailored for specific applications. In this context, even iron-based MNS show extended circulation as well as diverse organ accumulation beyond liver, which otherwise renders MNS potentially toxic to liver function. We believe that MNS, including those based on iron oxides, have entered a renaissance era where intelligent synthesis, functionalization, stabilization, and targeting provide ample evidence for applications in localized cancer theranostics.

Keywords

Magnetic nanostructures Theranostics Thermal activation MR imaging T2 contrast agents 

References

  1. 1.
    Kim J, Piao Y, Hyeon T (2009) Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. Chem Soc Rev 38(2):372–390PubMedCrossRefGoogle Scholar
  2. 2.
    Sun C, Lee JSH, Zhang MQ (2008) Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev 60(11):1252–1265PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ho D, Sun XL, Sun SH (2011) Monodisperse magnetic nanoparticles for theranostic applications. Acc Chem Res 44(10):875–882PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Yoo D et al (2011) Theranostic magnetic nanoparticles. Acc Chem Res 44(10):863–874PubMedCrossRefGoogle Scholar
  5. 5.
    Veiseh O, Gunn JW, Zhang MQ (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 62(3):284–304PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Xu CJ, Sun SH (2013) New forms of superparamagnetic nanoparticles for biomedical applications. Adv Drug Deliv Rev 65(5):732–743PubMedCrossRefGoogle Scholar
  7. 7.
    Cole AJ, Yang VC, David AE (2011) Cancer theranostics: the rise of targeted magnetic nanoparticles. Trends Biotechnol 29(7):323–332PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Livingston JD (1981) A review of coercivity mechanisms. J Appl Phys 52(3):2544–2548CrossRefGoogle Scholar
  9. 9.
    Reddy LH et al (2012) Magnetic nanoparticles: design and characterization, toxicity and biocompatibility. Pharmaceutical and biomedical applications. Chem Rev 112(11):5818–5878PubMedCrossRefGoogle Scholar
  10. 10.
    McCarthy JR, Weissleder R (2008) Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv Drug Deliv Rev 60(11):1241–1251PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Misra RDK (2008) Magnetic nanoparticle carrier for targeted drug delivery: perspective, outlook and design. Mater Sci Technol 24(9):1011–1019CrossRefGoogle Scholar
  12. 12.
    Kievit FM, Zhang MQ (2011) Surface engineering of iron oxide nanoparticies for targeted cancer therapy. Acc Chem Res 44(10):853–862PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Jun YW, Lee JH, Cheon J (2008) Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. Angew Chem Int Ed 47(28):5122–5135CrossRefGoogle Scholar
  14. 14.
    Lee N, Hyeon T (2012) Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chem Soc Rev 41(7):2575–2589PubMedCrossRefGoogle Scholar
  15. 15.
    De M et al (2011) Hybrid magnetic nanostructures (MNS) for magnetic resonance imaging applications. Adv Drug Deliv Rev 63(14–15):1282–1299PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Caravan P et al (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99(9):2293–2352PubMedCrossRefGoogle Scholar
  17. 17.
    Caravan P (2006) Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chem Soc Rev 35(6):512–523PubMedCrossRefGoogle Scholar
  18. 18.
    Frullano L, Meade TJ (2007) Multimodal MRI contrast agents. J Biol Inorg Chem 12(7):939–949PubMedCrossRefGoogle Scholar
  19. 19.
    Na HB, Hyeon T (2009) Nanostructured T1 MRI contrast agents. J Mater Chem 19(35):6267–6273CrossRefGoogle Scholar
  20. 20.
    Na HB, Song IC, Hyeon T (2009) Inorganic nanoparticles for MRI contrast agents. Adv Mater 21(21):2133–2148CrossRefGoogle Scholar
  21. 21.
    Hahn PF et al (1990) 1st clinical-trial of a new superparamagnetic iron-oxide for use as an oral gastrointestinal contrast agent in MR imaging. Radiology 175(3):695–700PubMedCrossRefGoogle Scholar
  22. 22.
    Reimer P, Balzer T (2003) Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 13(6):1266–1276PubMedGoogle Scholar
  23. 23.
    Koenig SH, Kellar KE (1995) Theory of 1/T1 and 1/T2 NMRD profiles of solutions of magnetic nanoparticles. Magn Reson Med 34(2):227–233PubMedCrossRefGoogle Scholar
  24. 24.
    Jordan A et al (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
  25. 25.
    Fortin JP et al (2007) Size-sorted anionic iron oxide nanomagnets as colloidal mediators for magnetic hyperthermia. J Am Chem Soc 129(9):2628–2635PubMedCrossRefGoogle Scholar
  26. 26.
    Hergt R, Dutz S (2007) Magnetic particle hyperthermia-biophysical limitations of a visionary tumour therapy. J Magn Magn Mater 311(1):187–192CrossRefGoogle Scholar
  27. 27.
    Jun YW et al (2005) Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J Am Chem Soc 127(16):5732–5733PubMedCrossRefGoogle Scholar
  28. 28.
    Laurent S et al (2008) Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 108(6):2064–2110PubMedCrossRefGoogle Scholar
  29. 29.
    Roca AG et al (2009) Progress in the preparation of magnetic nanoparticles for applications in biomedicine. J Phys D Appl Phys 42(22):224002Google Scholar
  30. 30.
    Massart R (1981) Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans Magn 17(2):1247–1248CrossRefGoogle Scholar
  31. 31.
    Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26(18):3995–4021PubMedCrossRefGoogle Scholar
  32. 32.
    Loo AL et al (2008) Synthesis of magnetic nanoparticles in bicontinuous microemulsions. Effect of surfactant concentration. J Mater Sci 43(10):3649–3654CrossRefGoogle Scholar
  33. 33.
    Murray CB, Kagan CR, Bawendi MG (2000) Synthesis and characterization of monodisperse nanocrystals and close-packed nanocrystal assemblies. Annu Rev Mater Sci 30:545–610CrossRefGoogle Scholar
  34. 34.
    Park J et al (2004) Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater 3(12):891–895PubMedCrossRefGoogle Scholar
  35. 35.
    Wang YXJ, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11(11):2319–2331PubMedCrossRefGoogle Scholar
  36. 36.
    Jung CW, Jacobs P (1995) Physical and chemical-properties of superparamagnetic iron-oxide MR contrast agents—ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging 13(5):661–674PubMedCrossRefGoogle Scholar
  37. 37.
    Lee JH et al (2006) Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma. Angew Chem Int Ed 45(48):8160–8162CrossRefGoogle Scholar
  38. 38.
    Lee JH et al (2007) Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med 13(1):95–99PubMedCrossRefGoogle Scholar
  39. 39.
    Tong S et al (2010) Coating optimization of superparamagnetic iron oxide nanoparticles for high T-2 relaxivity. Nano Lett 10(11):4607–4613PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Lee N et al (2011) Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets. Proc Natl Acad Sci USA 108(7):2662–2667PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Barcena C et al (2008) Zinc ferrite nanoparticles as MRI contrast agents. Chem Commun 19:2224–2226CrossRefGoogle Scholar
  42. 42.
    Jang JT et al (2009) Critical enhancements of MRI contrast and hyperthermic effects by dopant-controlled magnetic nanoparticles. Angew Chem Int Ed 48(7):1234–1238CrossRefGoogle Scholar
  43. 43.
    Seo WS et al (2006) FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents. Nat Mater 5(12):971–976PubMedCrossRefGoogle Scholar
  44. 44.
    Lacroix LM et al (2011) Stable single-crystalline body centered cubic Fe nanoparticles. Nano Lett 11(4):1641–1645PubMedCrossRefGoogle Scholar
  45. 45.
    Lee H, Yoon TJ, Weissleder R (2009) Ultrasensitive detection of bacteria using core-shell nanoparticles and an NMR-filter system. Angew Chem Int Ed 48(31):5657–5660CrossRefGoogle Scholar
  46. 46.
    Yoon TJ et al (2011) Highly magnetic core-shell nanoparticles with a unique magnetization mechanism. Angew Chem Int Ed 50(20):4663–4666CrossRefGoogle Scholar
  47. 47.
    Hu FQ et al (2010) High-performance nanostructured MR contrast probes. Nanoscale 2(10):1884–1891PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Hu FQ et al (2010) Highly dispersible, superparamagnetic magnetite nanoflowers for magnetic resonance imaging. Chem Commun 46(1):73–75CrossRefGoogle Scholar
  49. 49.
    Morales MP et al (1999) Surface and internal spin canting in gamma-Fe2O3 nanoparticles. Chem Mater 11(11):3058–3064CrossRefGoogle Scholar
  50. 50.
    Puntes VF, Krishnan KM, Alivisatos AP (2001) Colloidal nanocrystal shape and size control: the case of cobalt. Science 291(5511):2115–2117PubMedCrossRefGoogle Scholar
  51. 51.
    Cordente N et al (2001) Synthesis and magnetic properties of nickel nanorods. Nano Lett 1(10):565–568CrossRefGoogle Scholar
  52. 52.
    Desvaux C et al (2005) Multimillimetre-large superlattices of air-stable iron-cobalt nanoparticles. Nat Mater 4(10):750–753PubMedCrossRefGoogle Scholar
  53. 53.
    Schutz-Sikma EA et al (2011) Probing the chemical stability of mixed ferrites: implications for magnetic resonance contrast agent design. Chem Mater 23(10):2657–2664CrossRefGoogle Scholar
  54. 54.
    Colombo M et al (2012) Biological applications of magnetic nanoparticles. Chem Soc Rev 41(11):4306–4334PubMedCrossRefGoogle Scholar
  55. 55.
    Bao YP, Krishnan KM (2005) Preparation of functionalized and gold-coated cobalt nanocrystals for biomedical applications. J Magn Magn Mater 293(1):15–19CrossRefGoogle Scholar
  56. 56.
    Peng S et al (2006) Synthesis and stabilization of monodisperse Fe nanoparticles. J Am Chem Soc 128(33):10676–10677PubMedCrossRefGoogle Scholar
  57. 57.
    Ni XM et al (2010) Silica-coated iron nanoparticles: shape-controlled synthesis, magnetism and microwave absorption properties. Mater Chem Phys 120(1):206–212CrossRefGoogle Scholar
  58. 58.
    Cozzoli PD, Pellegrino T, Manna L (2006) Synthesis, properties and perspectives of hybrid nanocrystal structures. Chem Soc Rev 35(11):1195–1208PubMedCrossRefGoogle Scholar
  59. 59.
    Donega CD (2011) Synthesis and properties of colloidal heteronanocrystals. Chem Soc Rev 40(3):1512–1546CrossRefGoogle Scholar
  60. 60.
    Gao JH, Gu HW, Xu B (2009) Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. Acc Chem Res 42(8):1097–1107PubMedCrossRefGoogle Scholar
  61. 61.
    Xu CJ, Wang BD, Sun SH (2009) Dumbbell-like Au-Fe3O4 nanoparticles for target-specific platin delivery. J Am Chem Soc 131(12):4216–4217PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Gu HW et al (2004) Facile one-pot synthesis of bifunctional heterodimers of nanoparticles: a conjugate of quantum dot and magnetic nanoparticles. J Am Chem Soc 126(18):5664–5665PubMedCrossRefGoogle Scholar
  63. 63.
    Kwon KW, Shim M (2005) gamma-Fe2O3/II-VI sulfide nanocrystal heterojunctions. J Am Chem Soc 127(29):10269–10275PubMedCrossRefGoogle Scholar
  64. 64.
    Choi JH et al (2007) Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes. Nano Lett 7(4):861–867PubMedCrossRefGoogle Scholar
  65. 65.
    Gao JH et al (2007) Fluorescent magnetic nanocrystals by sequential addition of reagents in a one-pot reaction: a simple preparation for multifunctional nanostructures. J Am Chem Soc 129(39):11928–11935PubMedCrossRefGoogle Scholar
  66. 66.
    Pittet MJ et al (2006) Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles. Nat Protoc 1(1):73–79PubMedCrossRefGoogle Scholar
  67. 67.
    Wang DS et al (2004) Superparamagnetic Fe2O3 Beads-CdSe/ZnS quantum dots core-shell nanocomposite particles for cell separation. Nano Lett 4(3):409–413CrossRefGoogle Scholar
  68. 68.
    Choi JS et al (2010) Self-confirming “AND” logic nanoparticles for fault-free MRI. J Am Chem Soc 132(32):11015–11017PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Gupta AK et al (2007) Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomedicine 2(1):23–39PubMedCrossRefGoogle Scholar
  70. 70.
    Kohler N, Fryxell GE, Zhang MQ (2004) A bifunctional poly(ethylene glycol) silane immobilized on metallic oxide-based nanoparticles for conjugation with cell targeting agents. J Am Chem Soc 126(23):7206–7211PubMedCrossRefGoogle Scholar
  71. 71.
    Xie J et al (2007) Controlled PEGylation of monodisperse Fe3O4 nanoparticles for reduced non-specific uptake by macrophage cells. Adv Mater 19(20):3163–3166Google Scholar
  72. 72.
    Mornet S, Portier J, Duguet E (2005) A method for synthesis and functionalization of ultrasmall superparamagnetic covalent carriers based on maghemite and dextran. J Magn Magn Mater 293(1):127–134CrossRefGoogle Scholar
  73. 73.
    Kim DH et al (2009) Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia. J Biomed Mater Res Part A 88A(1):1–11CrossRefGoogle Scholar
  74. 74.
    Pradhan P et al (2010) Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Controlled Release 142(1):108–121CrossRefGoogle Scholar
  75. 75.
    Wang LY et al (2008) Core@shell nanomaterials: gold-coated magnetic oxide nanoparticles. J Mater Chem 18(23):2629–2635CrossRefGoogle Scholar
  76. 76.
    Ma DL et al (2007) Superparamagnetic Fe(x)Oy@SiO2 core-shell nanostructures: controlled synthesis and magnetic characterization. J Phys Chem C 111(5):1999–2007CrossRefGoogle Scholar
  77. 77.
    Fuertges F, Abuchowski A (1990) The clinical efficacy of poly(ethylene glycol)-modified proteins. J Controlled Release 11(1–3):139–148CrossRefGoogle Scholar
  78. 78.
    Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2(3):214–221PubMedCrossRefGoogle Scholar
  79. 79.
    Lutz JF et al (2006) One-pot synthesis of PEGylated ultrasmall iron-oxide nanoparticles and their in vivo evaluation as magnetic resonance imaging contrast agents. Biomacromolecules 7(11):3132–3138PubMedCrossRefGoogle Scholar
  80. 80.
    Kim SW et al (2005) Phosphine oxide polymer for water-soluble nanoparticles. J Am Chem Soc 127(13):4556–4557PubMedCrossRefGoogle Scholar
  81. 81.
    Xu CJ et al (2004) Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles. J Am Chem Soc 126(32):9938–9939PubMedCrossRefGoogle Scholar
  82. 82.
    Amstad E et al (2009) Ultrastable iron oxide nanoparticle colloidal suspensions using dispersants with catechol-derived anchor groups. Nano Lett 9(12):4042–4048PubMedCrossRefGoogle Scholar
  83. 83.
    Jaiswal MK et al (2014) Thermoresponsive magnetic hydrogels as theranostic nanoconstructs. ACS Appl Mater Interfaces 6(9):6237–6247PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Molday RS, Mackenzie D (1982) Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic separation of cells. J Immunol Methods 52(3):353–367PubMedCrossRefGoogle Scholar
  85. 85.
    Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452(7187):580–589PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Medarova Z et al (2007) In vivo imaging of siRNA delivery and silencing in tumors. Nat Med 13(3):372–377PubMedCrossRefGoogle Scholar
  87. 87.
    Kumar M et al (2010) Image-guided breast tumor therapy using a small interfering RNA nanodrug. Cancer Res 70(19):7553–7561PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    DeVita VT, Chu E (2008) A history of cancer chemotherapy. Cancer Res 68(21):8643–8653PubMedCrossRefGoogle Scholar
  89. 89.
    Kohler N et al (2006) Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small 2(6):785–792PubMedCrossRefGoogle Scholar
  90. 90.
    Sun C et al (2008) In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nanoprobes. Small 4(3):372–379PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Bautista MC et al (2005) Surface characterisation of dextran-coated iron oxide nanoparticles prepared by laser pyrolysis and coprecipitation. J Magn Magn Mater 293(1):20–27CrossRefGoogle Scholar
  92. 92.
    Wunderbaldinger P, Josephson L, Weissleder R (2002) Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR contrast agents. Acad Radiol 9:S304–S306PubMedCrossRefGoogle Scholar
  93. 93.
    Li W et al (2005) First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Reson Imaging 21(1):46–52PubMedCrossRefGoogle Scholar
  94. 94.
    Lu Y et al (2002) Modifying the surface properties of superparamagnetic iron oxide nanoparticles through a sol-gel approach. Nano Lett 2(3):183–186CrossRefGoogle Scholar
  95. 95.
    Pinho SLC et al (2010) Fine tuning of the relaxometry of gamma-Fe2O3@SiO2 nanoparticles by tweaking the silica coating thickness. ACS Nano 4(9):5339–5349PubMedCrossRefGoogle Scholar
  96. 96.
    Liong M et al (2008) Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2(5):889–896PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Aslam M, Li S, Dravid VP (2007) Controlled synthesis and stability of Co@SiO2 aqueous colloids. J Am Ceram Soc 90(3):950–956CrossRefGoogle Scholar
  98. 98.
    Yoo JW, Chambers E, Mitragotri S (2010) Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Curr Pharm Des 16(21):2298–2307PubMedCrossRefGoogle Scholar
  99. 99.
    Chouly C et al (1996) Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. J Microencapsul 13(3):245–255PubMedCrossRefGoogle Scholar
  100. 100.
    Gupta AK, Wells S (2004) Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans Nanobiosci 3(1):66–73CrossRefGoogle Scholar
  101. 101.
    Decuzzi P et al (2006) The effective dispersion of nanovectors within the tumor microvasculature. Ann Biomed Eng 34(4):633–641PubMedCrossRefGoogle Scholar
  102. 102.
    Chertok B, David AE, Yang VC (2010) Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. Biomaterials 31(24):6317–6324PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Sun CR et al (2010) PEG-mediated synthesis of highly dispersive multifunctional superparamagnetic nanoparticles: their physicochemical properties and function in vivo. ACS Nano 4(4):2402–2410PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Larsen EKU et al (2009) Size-dependent accumulation of PEGylated silane-coated magnetic iron oxide nanoparticles in murine tumors. ACS Nano 3(7):1947–1951PubMedCrossRefGoogle Scholar
  105. 105.
    Yallapu MM et al (2010) PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications. Pharm Res 27(11):2283–2295PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Longmire M, Choyke PL, Kobayashi H (2008) Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine 3(5):703–717PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Gratton SEA et al (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105(33):11613–11618PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Moghimi SM (1995) Exploiting bone-marrow microvascular structure for drug-delivery and future therapies. Adv Drug Deliv Rev 17(1):61–73CrossRefGoogle Scholar
  109. 109.
    Moghimi SM (1995) Mechanisms of splenic clearance of blood-cells and particles—towards development of new splenotropic agents. Adv Drug Deliv Rev 17(1):103–115CrossRefGoogle Scholar
  110. 110.
    Villanueva A et al (2009) The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells. Nanotechnology 20(11):115103Google Scholar
  111. 111.
    Maeda H et al (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Controlled Release 65(1–2):271–284CrossRefGoogle Scholar
  112. 112.
    Jain RK (1999) Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng 1:241–263PubMedCrossRefGoogle Scholar
  113. 113.
    Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63(3):136–151PubMedCrossRefGoogle Scholar
  114. 114.
    Prabhakar U et al (2013) Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res 73(8):2412–2417PubMedCentralPubMedCrossRefGoogle Scholar
  115. 115.
    Zhang Y, Kohler N, Zhang MQ (2002) Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 23(7):1553–1561PubMedCrossRefGoogle Scholar
  116. 116.
    Sinha R et al (2006) Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol Cancer Ther 5(8):1909–1917PubMedCrossRefGoogle Scholar
  117. 117.
    Kohler N et al (2005) Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells. Langmuir 21(19):8858–8864PubMedCrossRefGoogle Scholar
  118. 118.
    Sun C, Sze R, Zhang MQ (2006) Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J Biomed Mater Res Part A 78A(3):550–557CrossRefGoogle Scholar
  119. 119.
    Montet X, Weissleder R, Josephson L (2006) Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas. Bioconjug Chem 17(4):905–911PubMedCrossRefGoogle Scholar
  120. 120.
    Gunn J et al (2008) A multimodal targeting nanoparticle for selectively labeling T cells. Small 4(6):712–715PubMedCentralPubMedCrossRefGoogle Scholar
  121. 121.
    Hong S et al (2007) The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem Biol 14(1):107–115PubMedCrossRefGoogle Scholar
  122. 122.
    Chertok B et al (2007) Glioma selectivity of magnetically targeted nanoparticles: a role of abnormal tumor hydrodynamics. J Controlled Release 122(3):315–323CrossRefGoogle Scholar
  123. 123.
    Dobson J (2006) Magnetic nanoparticles for drug delivery. Drug Dev Res 67(1):55–60CrossRefGoogle Scholar
  124. 124.
    Wilson MW et al (2004) Hepatocellular carcinoma: regional therapy with a magnetic targeted carrier bound to doxorubicin in a dual MR imaging/conventional angiography suite—initial experience with four patients. Radiology 230(1):287–293PubMedCrossRefGoogle Scholar
  125. 125.
    Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17(7):484–499PubMedCrossRefGoogle Scholar
  126. 126.
    Artemov D et al (2003) MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med 49(3):403–408PubMedCrossRefGoogle Scholar
  127. 127.
    Hu FQ et al (2006) Preparation of biocompatible magnetite nanocrystals for in vivo magnetic resonance detection of cancer. Adv Mater 18(19):2553–2556Google Scholar
  128. 128.
    Xie J et al (2008) Ultrasmall c(RGDyK)-coated Fe(3)O(4) nanoparticles and their specific targeting to integrin alpha(v)beta(3)-rich tumor cells. J Am Chem Soc 130(24):7542Google Scholar
  129. 129.
    Bulte JWM et al (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19(12):1141–1147PubMedCrossRefGoogle Scholar
  130. 130.
    Frank JA et al (2003) Clinically applicable labeling of mammalian and stem cells by combining; superparamagnetic iron oxides and transfection agents. Radiology 228(2):480–487PubMedCrossRefGoogle Scholar
  131. 131.
    Bulte JWM (2009) In vivo MRI cell tracking: clinical studies. Am J Roentgenol 193(2):314–325CrossRefGoogle Scholar
  132. 132.
    Berman SMC, Walczak P, Bulte JWM (2011) Tracking stem cells using magnetic nanoparticles. Wiley Interdisc Rev Nanomed Nanobiotechnol 3(4):343–355CrossRefGoogle Scholar
  133. 133.
    Ahrens ET, Bulte JWM (2013) Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol 13(10):755–763PubMedCrossRefGoogle Scholar
  134. 134.
    Srivastava AK, Bulte JWM (2014) Seeing stem cells at work in vivo. Stem Cell Rev Rep 10(1):127–144CrossRefGoogle Scholar
  135. 135.
    Kircher MF et al (2003) In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 63(20):6838–6846PubMedGoogle Scholar
  136. 136.
    Daldrup-Link HE et al (2005) In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging. Eur Radiol 15(1):4–13PubMedCrossRefGoogle Scholar
  137. 137.
    Anderson SA et al (2004) Magnetic resonance imaging of labeled T-Cells in a mouse model of multiple sclerosis. Ann Neurol 55(5):654–659PubMedCrossRefGoogle Scholar
  138. 138.
    Berman SMC et al (2013) Cell motility of neural stem cells is reduced after SPIO-labeling, which is mitigated after exocytosis. Magn Reson Med 69(1):255–262CrossRefGoogle Scholar
  139. 139.
    de Vries IJM et al (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23(11):1407–1413PubMedCrossRefGoogle Scholar
  140. 140.
    Verdijk P et al (2007) Sensitivity of magnetic resonance imaging of dendritic cells for in vivo tracking of cellular cancer vaccines. Int J Cancer 120(5):978–984PubMedCrossRefGoogle Scholar
  141. 141.
    Verdijk P et al (2009) Limited amounts of dendritic cells migrate into the T-Cell area of lymph nodes but have high immune activating potential in melanoma patients. Clin Cancer Res 15(7):2531–2540PubMedCrossRefGoogle Scholar
  142. 142.
    Schuurhuis DH et al (2009) In situ expression of tumor antigens by messenger RNA-electroporated dendritic cells in lymph nodes of melanoma patients. Cancer Res 69(7):2927–2934PubMedCrossRefGoogle Scholar
  143. 143.
    Cruz LJ et al (2011) multimodal imaging of nanovaccine carriers targeted to human dendritic cells. Mol Pharm 8(2):520–531PubMedCrossRefGoogle Scholar
  144. 144.
    Janowski M et al (2014) Long-term MRI cell tracking after intraventricular delivery in a patient with global cerebral ischemia and prospects for magnetic navigation of stem cells within the CSF. PLoS ONE 9(6):e97631Google Scholar
  145. 145.
    Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53(2):283–318PubMedGoogle Scholar
  146. 146.
    Huang J et al (2010) Effects of nanoparticle size on cellular uptake and liver MRI with polyvinylpyrrolidone-coated iron oxide nanoparticles. ACS Nano 4(12):7151–7160PubMedCentralPubMedCrossRefGoogle Scholar
  147. 147.
    Joshi HM et al (2009) Effects of shape and size of cobalt ferrite nanostructures on their MRI contrast and thermal activation. J Phys Chem C 113(41):17761–17767CrossRefGoogle Scholar
  148. 148.
    Zhao ZH et al (2013) Octapod iron oxide nanoparticles as high-performance T-2 contrast agents for magnetic resonance imaging. Nat Commun 4:2266Google Scholar
  149. 149.
    Berret JF et al (2006) Controlled clustering of superparamagnetic nanoparticles using block copolymers: design of new contrast agents for magnetic resonance imaging. J Am Chem Soc 128(5):1755–1761PubMedCrossRefGoogle Scholar
  150. 150.
    Lee JE et al (2010) Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery. J Am Chem Soc 132(2):552–557PubMedCrossRefGoogle Scholar
  151. 151.
    Barick KC et al (2009) Nanoscale assembly of amine-functionalized colloidal iron oxide. J Magn Magn Mater 321(10):1529–1532PubMedCentralPubMedCrossRefGoogle Scholar
  152. 152.
    LaConte LEW et al (2007) Coating thickness of magnetic iron oxide nanoparticles affects R-2 relaxivity. J Magn Reson Imaging 26(6):1634–1641PubMedCrossRefGoogle Scholar
  153. 153.
    Gao JH et al (2008) Multifunctional yolk-shell nanoparticles: a potential MRI contrast and anticancer agent. J Am Chem Soc 130(35):11828–11833PubMedCrossRefGoogle Scholar
  154. 154.
    Mahmoudi M et al (2011) Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev 63(1–2):24–46PubMedCrossRefGoogle Scholar
  155. 155.
    Pollert E et al (2009) Search of new core materials for magnetic fluid hyperthermia: preliminary chemical and physical issues. Prog Solid State Chem 37(1):1–14CrossRefGoogle Scholar
  156. 156.
    Lacroix LM et al (2009) Magnetic hyperthermia in single-domain monodisperse FeCo nanoparticles: evidences for Stoner-Wohlfarth behavior and large losses. J Appl Phys 105(2):023911Google Scholar
  157. 157.
    Mehdaoui B et al (2010) Large specific absorption rates in the magnetic hyperthermia properties of metallic iron nanocubes. J Magn Magn Mater 322(19):L49–L52CrossRefGoogle Scholar
  158. 158.
    Franchini MC et al (2010) Bovine serum albumin-based magnetic nanocarrier for MRI diagnosis and hyperthermic therapy: a potential theranostic approach against cancer. Small 6(3):366–370CrossRefGoogle Scholar
  159. 159.
    Lee J-H et al (2011) Exchange-coupled magnetic nanoparticles for efficient heat induction. Nat Nano 6(7):418–422CrossRefGoogle Scholar
  160. 160.
    Yoo D et al (2012) Double-effector nanoparticles: a synergistic approach to apoptotic hyperthermia. Angew Chem Int Ed 51(50):12482–12485CrossRefGoogle Scholar
  161. 161.
    Mykhaylyk O et al (2008) siRNA delivery by magnetofection. Curr Opin Mol Ther 10(5):493–505PubMedGoogle Scholar
  162. 162.
    McBain SC et al (2008) Magnetic nanoparticles as gene delivery agents: enhanced transfection in the presence of oscillating magnet arrays. Nanotechnology 19(40):405102Google Scholar
  163. 163.
    Petri-Fink A et al (2008) Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. Eur J Pharm Biopharm 68(1):129–137PubMedCrossRefGoogle Scholar
  164. 164.
    Kievit FM et al (2009) PEI-PEG-Chitosan-copolymer-coated iron oxide nanoparticles for safe gene delivery: synthesis, complexation, and transfection. Adv Funct Mater 19(14):2244–2251PubMedCentralPubMedCrossRefGoogle Scholar
  165. 165.
    Kievit FM et al (2010) Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. ACS Nano 4(8):4587–4594PubMedCentralPubMedCrossRefGoogle Scholar
  166. 166.
    Shin JM et al (2009) Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angew Chem Int Ed 48(2):321–324CrossRefGoogle Scholar
  167. 167.
    Cheng K et al (2009) Porous hollow Fe3O4 nanoparticles for targeted delivery and controlled release of cisplatin. J Am Chem Soc 131(30):10637–10644PubMedCentralPubMedCrossRefGoogle Scholar
  168. 168.
    Jain TK et al (2008) Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging. Biomaterials 29(29):4012–4021PubMedCentralPubMedCrossRefGoogle Scholar
  169. 169.
    Thomas CR et al (2010) Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J Am Chem Soc 132(31):10623–10625PubMedCrossRefGoogle Scholar
  170. 170.
    Purushotham S, Ramanujan RV (2010) Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy. Acta Biomater 6(2):502–510PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Vikas Nandwana
    • 1
  • Mrinmoy De
    • 2
  • Shihyao Chu
    • 3
  • Manish Jaiswal
    • 4
  • Matt Rotz
    • 5
  • Thomas J. Meade
    • 5
  • Vinayak P. Dravid
    • 1
  1. 1.Department of Materials Science and EngineeringNorthwestern UniversityEvanstonUSA
  2. 2.Department of ChemistryIndian Institute of ScienceBengaluruIndia
  3. 3.Sandia National LaboratoryAlbuquerqueUSA
  4. 4.Department of Biomedical EngineeringTexas A&M UniversityCollege StationUSA
  5. 5.Departments of Chemistry, Molecular BioSciences, Neurobiology, Biomedical Engineering, and RadiologyNorthwestern UniversityEvanstonUSA

Personalised recommendations