The purpose of this study was to develop a specific targeting magnetic nanoparticle probe for magnetic resonance imaging and therapy in the form of local hyperthermia. Carboxymethyl dextran–coated ultrasmall superparamagnetic iron oxide nanoparticles with carboxyl groups were coupled to cyclic arginine-glycine-aspartic peptides for integrin αvβ3 targeting. The particle size, magnetic properties, heating effect, and stability of the arginine-glycine-aspartic–ultrasmall superparamagnetic iron oxide were measured. The arginine-glycine-aspartic–ultrasmall superparamagnetic iron oxide demonstrates excellent stability and fast magneto-temperature response. Magnetic resonance imaging signal intensity of Bcap37 cells incubated with arginine-glycine-aspartic–ultrasmall superparamagnetic iron oxide was significantly decreased compared with that incubated with plain ultrasmall superparamagnetic iron oxide. The preferential uptake of arginine-glycine-aspartic–ultrasmall superparamagnetic iron oxide by target cells was further confirmed by Prussian blue staining and confocal laser scanning microscopy.
VeisehOGunnJWZhangMQ. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliver Rev2010; 2: 284–304.
2.
ChengFZhangMQ. Multifunctional magnetic nanoparticles for medical imaging applications. J Mater Chem2009; 19: 6258–6266.
3.
HuangXLZhuangJChenD. General strategy for designing functionalized magnetic microspheres for different bioapplications. Langmuir2009; 25: 11657–11663.
4.
McBainSCGriesenbachUXenariouS. Magnetic nanoparticles as gene delivery agents: enhanced transfection in the presence of oscillating magnet arrays. Nanotechnology2008; 19: 405102–405102.
5.
PimphaNChaleawlert-umponSChruewkamlowN. Preparation of anti-CD4 monoclonal antibody-conjugated magnetic poly(glycidyl methacrylate) particles and their application on CD4+ lymphocyte separation. Talanta2011; 84: 89–97.
6.
SunCLeeJSHZhangMQ. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliver Rev2008; 60: 1252–1265.
7.
WangYXJHussainSMKrestinGP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol2001; 11: 2319–2331.
8.
HarisinghaniMGBarentszJHahnPF. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. New Engl J Med2003; 348: 2491–2499.
9.
WeisslederRPittetMJ. Imaging in the era of molecular oncology. Nature2008; 452: 580–589.
10.
WeisslederR. Molecular imaging in cancer. Science2006; 312: 1168–1171.
11.
LiuGHongRYGuoL. Preparation, characterization and MRI application of carboxymethyl dextran coated magnetic nanoparticles. Appl Surf Sci2011; 257: 6711–6717.
12.
TartajPMoralesMPVeintemillas-VerdaguerSSynthesis, properties and biomedical applications of magnetic nanoparticles. In: BuschowKH (ed.) Handbook of magnetic materialsVol. 16. Amsterdam: Elsevier, 2006, pp. 403–482.
13.
WangYMCaoXLiuGH. Synthesis of Fe3O4 magnetic fluid used for magnetic resonance imaging and hyperthermia. J Magn Magn Mater2011; 323: 2953–2959.
14.
KiesslingFHuppertJZhangCF. RGD-labeled USPIO inhibits adhesion and endocytotic activity of αvβ3-integrin-expressing glioma cells and only accumulates in the vascular tumor compartment. Radiology2009; 253: 462–469.
15.
CaiWWuYChenK. In vitro and in vivo characterization for 64 Cu-labeled Abegrin, a humanized monoclonal antibody against integrin αvβ3. Cancer Res2006; 66: 9673–9681.
16.
TemmingKSchiffelersRMMolemaG. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Update2005; 8: 381–402.
17.
FriedlanderMTheesfeldCLSugitaM. Involvement of integrins αvβ3 and αvβ5 in ocular neovascular diseases. Proc Natl Acad Sci1996; 93: 9764–9769.
18.
KesslerTBiekerRPadróT. Inhibition of tumor growth by RGD peptide-directed delivery of truncated tissue factor to the tumor vasculature. Clin Cancer Res2005; 11: 6317–6324.
19.
HumphriesMJ. The LDV peptide motif: its role in integrin-ligand binding. Top Mol Med1995; 1: 27–35.
20.
DechantsreiterMAPlankerEMathaB. N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists. J Med Chem1999; 42: 3033–3340.
21.
ZhangCFJugoldMWoenneEC. Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res2007; 67: 1555–1562.
22.
GurrathMMullerGKesslerH. Conformation activity studies of rationally designed potent antiadhesive RGD peptides. Eur J Biochem1992; 210: 911–921.
23.
ChenFVeisehOKievitF. Functionalization of iron oxide magnetic nanoparticles with targeting ligands: their physicochemical properties and in vivo behavior. Nanomedicine2010; 9: 1357–1369.
24.
Petri-FinkASteitzBFinkaA. Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. Eur J Pharm Biopharm2008; 68: 129–137.
25.
HongRYLiJHLiHZ. Synthesis of Fe3O4 nanoparticles without inert gas protection used as precursors of magnetic fluids. J Magn Magn Mater2008; 320: 1605–1614.
26.
YamauraMCamiloRLSampaioLC. Preparation and characterization of (3-aminopropyl) triethoxysilane-coated magnetite nanoparticles. J Magn Magn Mater2004; 279: 210–217.
27.
ChenYQianZZhangZC. Novel preparation of magnetite/polystyrene composite particles via inverse emulsion polymerization. Colloids Surf A2008; 312: 209–213.
28.
LiuGHongRYGuoL. Exothermic effect of dextran-coated Fe3O4 magnetic fluid and its compatibility with blood. Colloid Surface A2011; 380: 327–333.
29.
FalkMHIsselsRD. Hyperthermia in oncology. Int J Hyperthermia2001; 17: 1–18.
30.
QuJMLiuGWangYM. Preparation of Fe3O4-chitosan nanoparticles used for hyperthermia. Adv Powder Technol2010; 21: 461–467.
31.
ChenKYapLPParkR. A Cy5.5-labeled phage-displayed peptide probe for near-infrared fluorescence imaging of tumor vasculature in living mice. Amino Acids2012; 42: 1329–1337.
