Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging of cancer

Abstract

Superparamagnetic iron oxide (SPIO) nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility. A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles, such as surface-coated, targeted ligand-conjugated, and/or drug-loaded SPIO nanoparticles, as powerful tools for targeted imaging and therapy. Moreover, the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment. In the present review, we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis, targeted therapy, and cancer imaging.

Keywords

nanoparticles / superparamagnetic iron oxide / targeted therapy / molecular imaging / cancer

References

[1] Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discov Today 2010; 15(19-20): 842–850

[2] Wang X, Yang L, Chen ZG, Shin DM. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin 2008; 58(2): 97–110

[3] Alam S, Anand C, Ariga K, Mori T, Vinu A. Unusual magnetic properties of size-controlled iron oxide nanoparticles grown in a nanoporous matrix with tunable pores. Angew Chem Int Ed Engl 2009; 48(40): 7358–7361

[4] Yang X, Hong H, Grailer JJ, Rowland IJ, Javadi A, Hurley SA, Xiao Y, Yang Y, Zhang Y, Nickles RJ, Cai W, Steeber DA, Gong S. cRGD-functionalized, DOX-conjugated, and ⁶⁴Cu- labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials 2011; 32(17): 4151–4160

[5] Mahmoudi M, Sant S, Wang B, Laurent S, Sen T. Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev 2011; 63(1-2): 24–46

[6] Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010; 464(7291): 1067–1070

[7] Wilson DS, Dalmasso G, Wang L, Sitaraman SV, Merlin D, Murthy N. Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines. Nat Mater 2010; 9(11): 923–928

[8] Brower V. RNA interference advances to early-stage clinical trials. J Natl Cancer Inst 2010; 102(19): 1459–1461

[9] Sonvico F, Mornet S, Vasseur S, Dubernet C, Jaillard D, Degrouard J, Hoebeke J, Duguet E, Colombo P, Couvreur P. Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments. Bioconjug Chem 2005; 16(5): 1181–1188

[10] Pradhan P, Giri J, Rieken F, Koch C, Mykhaylyk O, Döblinger M, Banerjee R, Bahadur D, Plank C. Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release 2010; 142(1): 108–121

[11] Yang H, Zhuang Y, Sun Y, Dai A, Shi X, Wu D, Li F, Hu H, Yang S. Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. Biomaterials 2011; 32(20): 4584–4593

[12] Varallyay CG, Muldoon LL, Gahramanov S, Wu YJ, Goodman JA, Li X, Pike MM, Neuwelt EA. Dynamic MRI using iron oxide nanoparticles to assess early vascular effects of antiangiogenic versus corticosteroid treatment in a glioma model. J Cereb Blood Flow Metab 2009; 29(4): 853–860

[13] Xie H, Zhu Y, Jiang W, Zhou Q, Yang H, Gu N, Zhang Y, Xu H, Xu H, Yang X. Lactoferrin-conjugated superparamagnetic iron oxide nanoparticles as a specific MRI contrast agent for detection of brain glioma in vivo. Biomaterials 2011; 32(2): 495–502

[14] Lunov O, Syrovets T, Büchele B, Jiang X, Röcker C, Tron K, Nienhaus GU, Walther P, Mailänder V, Landfester K, Simmet T. The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages. Biomaterials 2010; 31(19): 5063–5071

[15] Talelli M, Rijcken CJ, Lammers T, Seevinck PR, Storm G, van Nostrum CF, Hennink WE. Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for image-guided drug delivery. Langmuir 2009; 25(4): 2060–2067

[16] Lunov O, Zablotskii V, Syrovets T, Röcker C, Tron K, Nienhaus GU, Simmet T. Modeling receptor-mediated endocytosis of polymer-functionalized iron oxide nanoparticles by human macrophages. Biomaterials 2011; 32(2): 547–555

[17] Beduneau A, Ma Z, Grotepas CB, Kabanov A, Rabinow BE, Gong N, Mosley RL, Dou H, Boska MD, Gendelman HE. Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles. PLoS ONE 2009; 4(2): e4343

[18] Landmark KJ, Dimaggio S, Ward J, Kelly C, Vogt S, Hong S, Kotlyar A, Myc A, Thomas TP, Penner-Hahn JE, Baker JR, Holl MM, Orr BG. Synthesis, characterization, and in vitro testing of superparamagnetic iron oxide nanoparticles targeted using folic acid-conjugated dendrimers. ACS Nano 2008; 2(4): 773–783

[19] Maeng JH, Lee DH, Jung KH, Bae YH, Park IS, Jeong S, Jeon YS, Shim CK, Kim W, Kim J, Lee J, Lee YM, Kim JH, Kim WH, Hong SS. Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 2010; 31(18): 4995–5006

[20] Rishton SA, Lu Y, Altman RA, Marley AC, Bian XP, Jahnes C, Viswanathan R, Xiao G, Gallagher WJ, Parkin SSP. Magnetic tunnel junctions fabricated at tenth-micron dimensions by electron beam lithography. Microelectron Eng 1997; 35(1-4): 249–252

[21] Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005; 26(18): 3995–4021

[22] Babes L, Denizot B, Tanguy G, Jallet P. Synthesis of iron oxide nanoparticles used as MRI contrast agents: a parametric study. J Colloid Interface Sci 1999; 212(2): 474–482

[23] Lee HY, Li Z, Chen K, Hsu AR, Xu C, Xie J, Sun S, Chen X. PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles. J Nucl Med 2008; 49(8): 1371–1379

[24] Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, Häfeli UO, Stroeve P. A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. Colloids Surf B Biointerfaces 2010; 75(1): 300–309

[25] Müller K, Skepper JN, Tang TY, Graves MJ, Patterson AJ, Corot C, Lancelot E, Thompson PW, Brown AP, Gillard JH. Atorvastatin and uptake of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) in human monocyte-macrophages: implications for magnetic resonance imaging. Biomaterials 2008; 29(17): 2656–2662

[26] Papaphilippou P, Loizou L, Popa NC, Han A, Vekas L, Odysseos A, Krasia-Christoforou T. Superparamagnetic hybrid micelles, based on iron oxide nanoparticles and well-defined diblock copolymers possessing beta-ketoester functionalities. Biomacromolecules 2009; 10(9): 2662–2671

[27] Munshi N, De TK, Maitra A. Size modulation of polymeric nanoparticles under controlled dynamics of microemulsion droplets. J Colloid Interface Sci 1997; 190(2): 387–391

[28] Takahashi M, Yoshino T, Matsunaga T. Surface modification of magnetic nanoparticles using asparagines-serine polypeptide designed to control interactions with cell surfaces. Biomaterials 2010; 31(18): 4952–4957

[29] Yu MK, Jeong YY, Park J, Park S, Kim JW, Min JJ, Kim K, Jon S. Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew Chem Int Ed 2008; 47(29): 5362–5365

[30] Prashant C, Dipak M, Yang CT, Chuang KH, Jun D, Feng SS. Superparamagnetic iron oxide—loaded poly(lactic acid)-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent. Biomaterials 2010; 31(21): 5588–5597

[31] Tsourkas A, Cheng ZL, Thorek DLJ. Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T(1) magnetic resonance imaging contrast agent. Angew Chem Int Ed 2010; 49(2): 346–350

[32] Sato A, Tamura Y, Sato N, Yamashita T, Takada T, Sato M, Osai Y, Okura M, Ono I, Ito A, Honda H, Wakamatsu K, Ito S, Jimbow K. Melanoma-targeted chemo-thermo-immuno (CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-magnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release. Cancer Sci 2010; 101(9): 1939–1946

[33] Dias AM, Hussain A, Marcos AS, Roque AC. A biotechnological perspective on the application of iron oxide magnetic colloids modified with polysaccharides. Biotechnol Adv 2011; 29(1): 142–155

[34] Griffiths SM, Singh N, Jenkins GJ,Williams PM, Orbaek AW, Barron AR, Wright CJ, Doak SH. Dextran coated ultrafine superparamagnetic iron oxide nanoparticles: compatibility with common fluorometric and colorimetric dyes. Anal Chem 2011; 83(10): 3778–3785

[35] Babic M, Horák D, Trchová M, Jendelová P, Glogarová K, Lesný P, Herynek V, Hájek M, Syková E. Poly(L-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjug Chem 2008; 19(3): 740–750

[36] Liao Z, Wang H, Lv R, Zhao P, Sun X, Wang S, Su W, Niu R, Chang J. Polymeric liposomes-coated superparamagnetic iron oxide nanoparticles as contrast agent for targeted magnetic resonance imaging of cancer cells. Langmuir 2011; 27(6): 3100–3105

[37] Amstad E, Zurcher S, Mashaghi A, Wong JY, Textor M, Reimhult E. Surface functionalization of single superparamagnetic iron oxide nanoparticles for targeted magnetic resonance imaging. Small 2009; 5(11): 1334–1342

[38] Storm G, Belliot SO, Daemen T, Lasic DD. Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Adv Drug Deliv Rev 1995; 17(1): 31–48

[39] Bazile D, Prud’homme C, Bassoullet MT, Marlard M, Spenlehauer G, Veillard M. Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system. J Pharm Sci 1995; 84(4): 493–498

[40] Liang G, Cai S, Zhang P, Peng Y, Chen H, Zhang S, Kong J. Magnetic relaxation switch and colorimetric detection of thrombin using aptamer-functionalized gold-coated iron oxide nanoparticles. Anal Chim Acta 2011; 689(2): 243–249

[41] Jain TK, Reddy MK, Morales MA, Leslie-Pelecky DL, Labhasetwar V. Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol Pharm 2008; 5(2): 316–327

[42] Chen B, Wu W, Wang X. Magnetic iron oxide nanoparticles for tumor-targeted therapy. Curr Cancer Drug Targets 2011; 11(2): 184–189

[43] Sato M, Yamashita T, Ohkura M, Osai Y, Sato A, Takada T, Matsusaka H, Ono I, Tamura Y, Sato N, Sasaki Y, Ito A, Honda H, Wakamatsu K, Ito S, Jimbow K. N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) is a nanoparticle for the targeted growth suppression of melanoma cells. J Invest Dermatol 2009; 129(9): 2233–2241

[44] Tang QS, Zhang DS, Cong XM, Wan ML, Jin LQ. Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression. Biomaterials 2008; 29(17): 2673–2679

[45] Scherer F, Anton M, Schillinger U, Henke J, Bergemann C, Krüger A, Gänsbacher B, Plank C. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther 2002; 9(2): 102–109

[46] Han L, Zhang A, Wang H, Pu P, Jiang X, Kang C, Chang J. Tat-BMPs-PAMAM conjugates enhance therapeutic effect of small interference RNA on U251 glioma cells in vitro and in vivo. Hum Gene Ther 2010; 21(4): 417–426

[47] Kamei K, Mukai Y, Kojima H, Yoshikawa T, Yoshikawa M, Kiyohara G, Yamamoto TA, Yoshioka Y, Okada N, Seino S, Nakagawa S. Direct cell entry of gold/iron-oxide magnetic nanoparticles in adenovirus mediated gene delivery. Biomaterials 2009; 30(9): 1809–1814

[48] Dilnawaz F, Singh A, Mohanty C, Sahoo SK. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 2010; 31(13): 3694–3706

[49] Yu MK, Jeong YY, Park J, Park S, Kim JW, Min JJ, Kim K, Jon S. Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew Chem Int Ed Engl 2008; 47(29): 5362–5365

[50] Maeng JH, Lee DH, Jung KH, Bae YH, Park IS, Jeong S, Jeon YS, Shim CK, Kim W, Kim J, Lee J, Lee YM, Kim JH, Kim WH, Hong SS. Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 2010; 31(18): 4995–5006

[51] Kievit FM, Wang FY, Fang C, Mok H, Wang K, Silber JR, Ellenbogen RG, Zhang M. Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro. J Control Release 2011; 152(1): 76–83

[52] Szakács G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006; 5(3): 219–234

[53] Arbab AS, Bashaw LA, Miller BR, Jordan EK, Lewis BK, Kalish H, Frank JA. Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology 2003; 229(3): 838–846

[54] Lee H, Lee E, Kim K, Jang NK, Jeong YY, Jon S. Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. J Am Chem Soc 2006; 128(22): 7383–7389

[55] Raynal I, Prigent P, Peyramaure S, Najid A, Rebuzzi C, Corot C. Macrophage endocytosis of superparamagnetic iron oxide nanoparticles: mechanisms and comparison of ferumoxides and ferumoxtran-10. Invest Radiol 2004; 39(1): 56–63

[56] Müller K, Skepper JN, Tang TY, Graves MJ, Patterson AJ, Corot C, Lancelot E, Thompson PW, Brown AP, Gillard JH. Atorvastatin and uptake of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) in human monocyte-macrophages: implications for magnetic resonance imaging. Biomaterials 2008; 29(17): 2656–2662

[57] Yang L, Mao H, Cao Z, Wang YA, Peng X, Wang X, Sajja HK, Wang L, Duan H, Ni C, Staley CA, Wood WC, Gao X, Nie S. Molecular imaging of pancreatic cancer in an animal model using targeted multifunctional nanoparticles. Gastroenterology 2009; 136(5): 1514–1525, e2

[58] Galanzha EI, Shashkov EV, Kelly T, Kim JW, Yang L, Zharov VP. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol 2009; 4(12): 855–860

Acknowledgements

This work was supported by the Natural Science Foundation of Hubei Province (Grant No. 2009HBKJH1).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg