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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2011, Vol. 5 Issue (4) : 379-387     DOI: 10.1007/s11684-011-0162-6
Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging of cancer
Liangqian Tong, Ming Zhao, Shu Zhu, Jing Chen()
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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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     
Corresponding Authors: Chen Jing,   
Issue Date: 05 December 2011
URL:     OR
Fig.1  The basic synthesis progress of SPIO nanoparticles. A, B, and C exhibit coprecipitation approach, thermal decomposition approach, and reverse micelle approach, respectively.
Fig.2  Core-shell structured SPIO nanoparticles: surface-modified nanoparticle A is coated with polymers, after which it can be used for targeted MRI contrast agents; nanoparticle B coated with polymers and loaded with drugs or genes can be used as an anticancer agent; surface-modified nanoparticle C coated with polymers and loaded with drugs or genes can be used as a diagnostic and therapeutic anticancer agent.
Fig.3  Principle of magnetic anticancer drug targeting. A represents the drug-loaded SPIO concentrates in the tumor site by EMF. B represents the SPIO concentrates in the tumor site by ligand-receptor reaction.
Fig.4  T1-weighted and T2-weighted magnetic resonance images of tumor injected with FeO-SiO(Gd-DTPA)-RGD NPs (yellow arrow indicates the location of tumor). T1 and T2 MR images of the tumor showed no obvious changes at 30 min post-injection, but they all showed significant enhancement at 24 h post-injection.
1 Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discov Today 2010; 15(19-20): 842–850
doi: 10.1016/j.drudis.2010.08.006 pmid:20727417
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
doi: 10.3322/CA.2007.0003 pmid:18227410
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
doi: 10.1002/anie.200901570 pmid:19725083
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 ??Cu- labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials 2011; 32(17): 4151–4160
doi: 10.1016/j.biomaterials.2011.02.006 pmid:21367450
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
doi: 10.1016/j.addr.2010.05.006 pmid:20685224
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
doi: 10.1038/nature08956 pmid:20305636
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
doi: 10.1038/nmat2859 pmid:20935658
8 Brower V. RNA interference advances to early-stage clinical trials. J Natl Cancer Inst 2010; 102(19): 1459–1461
doi: 10.1093/jnci/djq405 pmid:20870977
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
doi: 10.1021/bc050050z pmid:16173796
10 Pradhan P, Giri J, Rieken F, Koch C, Mykhaylyk O, D?blinger M, Banerjee R, Bahadur D, Plank C. Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release 2010; 142(1): 108–121
doi: 10.1016/j.jconrel.2009.10.002 pmid:19819275
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
doi: 10.1016/j.biomaterials.2011.03.018 pmid:21458063
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
doi: 10.1038/jcbfm.2008.162 pmid:19142191
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
doi: 10.1016/j.biomaterials.2010.09.024 pmid:20970851
14 Lunov O, Syrovets T, Büchele B, Jiang X, R?cker C, Tron K, Nienhaus GU, Walther P, Mail?nder 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
doi: 10.1016/j.biomaterials.2010.03.023 pmid:20381862
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
doi: 10.1021/la8036499 pmid:19166276
16 Lunov O, Zablotskii V, Syrovets T, R?cker 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
doi: 10.1016/j.biomaterials.2010.08.111 pmid:20880574
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
doi: 10.1371/journal.pone.0004343 pmid:19183814
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
doi: 10.1021/nn800034w pmid:19206610
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
doi: 10.1016/j.biomaterials.2010.02.068 pmid:20347138
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
doi: 10.1016/S0167-9317(96)00107-4
21 Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005; 26(18): 3995–4021
doi: 10.1016/j.biomaterials.2004.10.012 pmid:15626447
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
doi: 10.1006/jcis.1998.6053 pmid:10092379
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
doi: 10.2967/jnumed.108.051243 pmid:18632815
24 Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, H?feli 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
doi: 10.1016/j.colsurfb.2009.08.044 pmid:19781921
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
doi: 10.1016/j.biomaterials.2008.03.006 pmid:18377983
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
doi: 10.1021/bm9005936 pmid:19627141
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
doi: 10.1006/jcis.1997.4889 pmid:9241182
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
doi: 10.1016/j.biomaterials.2010.02.048 pmid:20363023
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
doi: 10.1002/anie.200800857
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
doi: 10.1016/j.biomaterials.2010.03.070 pmid:20434210
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
doi: 10.1111/j.1349-7006.2010.01623.x pmid:20594194
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
doi: 10.1016/j.biotechadv.2010.10.003 pmid:20959138
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 21469681
doi: 10.1021/ac200103x
35 Babic M, Horák D, Trchová M, Jendelová P, Glogarová K, Lesny 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
doi: 10.1021/bc700410z pmid:18288791
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
doi: 10.1021/la1050157
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
doi: 10.1002/smll.200801328 pmid:19242944
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
doi: 10.1016/0169-409X(95)00039-A
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
doi: 10.1002/jps.2600840420 pmid:7629743
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
doi: 10.1016/j.aca.2011.01.046 pmid:21397080
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
doi: 10.1021/mp7001285 pmid:18217714
42 Chen B, Wu W, Wang X. Magnetic iron oxide nanoparticles for tumor-targeted therapy. Curr Cancer Drug Targets 2011; 11(2): 184–189
doi: 10.2174/156800911794328475 pmid:21158723
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
doi: 10.1038/jid.2009.39 pmid:19295615
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
doi: 10.1016/j.biomaterials.2008.01.038 pmid:18396332
45 Scherer F, Anton M, Schillinger U, Henke J, Bergemann C, Krüger A, G?nsbacher B, Plank C. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther 2002; 9(2): 102–109
doi: 10.1038/ pmid:11857068
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
doi: 10.1089/hum.2009.087 pmid:19899955
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
doi: 10.1016/j.biomaterials.2008.12.015 pmid:19136151
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
doi: 10.1016/j.biomaterials.2010.01.057 pmid:20144478
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
doi: 10.1002/anie.200800857 pmid:18551493
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
doi: 10.1016/j.jconrel.2011.01.024 pmid:21277920
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
doi: 10.1038/nrd1984 pmid:16518375
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
doi: 10.1148/radiol.2293021215 pmid:14657318
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
doi: 10.1021/ja061529k pmid:16734494
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
doi: 10.1097/01.rli.0000101027.57021.28 pmid:14701989
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
doi: 10.1053/j.gastro.2009.01.006 pmid:19208341
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
doi: 10.1038/nnano.2009.333 pmid:19915570
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