title: Design, synthesis and in vitro characterization of fluorescent and paramagnetic CXCR4-targeted imaging agents.
abstract: The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core, encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the imaging of the CXCR4 receptor by magnetic resonance imaging (MRI).
authors.affiliation: Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Hammersmith Hospital, Imperial College London London, W12 0NN, UK.
authors.forename: Ole
authors.initials: O
authors.lastname: Tietz
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.forename: Graham
authors.initials: G
authors.lastname: Smith
authors.forename: Elham
authors.initials: E
authors.lastname: Shamsaei
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Bhakoo
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Long
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
keywords: CXCR4; T2 imaging; cyclopentapeptide; iron oxide nanoparticles; targeted nanoparticles; tumor MRI
references.citation: Biopolymers. 2007;88(2):279-89
references.pmid: 17167792
references.citation: Acta Radiol. 2012 Nov 1;53(9):1049-58
references.pmid: 23012484
references.citation: Cancer Res. 2004 Dec 1;64(23):8604-12
references.pmid: 15574767
references.citation: Acc Chem Res. 2011 Oct 18;44(10):842-52
references.pmid: 21661727
references.citation: Adv Mater. 2009;21:419-424
references.pmid: 19606281
references.citation: Clin Exp Metastasis. 2011 Dec;28(8):713-20
references.pmid: 21735100
references.citation: J Nucl Med. 2011 Jun;52(6):986-93
references.pmid: 21622896
references.citation: Cancer Res. 2010 May 15;70(10):3935-44
references.pmid: 20460522
references.citation: Bioconjug Chem. 2011 May 18;22(5):859-64
references.pmid: 21480671
references.citation: FEBS Lett. 2003 Aug 28;550(1-3):79-83
references.pmid: 12935890
references.citation: J Biomed Opt. 2011 Jan-Feb;16(1):016011
references.pmid: 21280917
references.citation: Small. 2013 May 27;9(9-10):1450-66
references.pmid: 23233377
references.citation: Chem Commun (Camb). 2007 Jan 28;(4):416-8
references.pmid: 17220989
references.citation: J Nucl Med. 2009 Jul;50(7):1124-30
references.pmid: 19525448
references.citation: Adv Drug Deliv Rev. 2011 Jan-Feb;63(1-2):24-46
references.pmid: 20685224
references.citation: Nat Nanotechnol. 2012 Oct;7(10):677-82
references.pmid: 22983492
references.citation: Lab Invest. 2004 Dec;84(12):1666-76
references.pmid: 15467730
references.citation: Curr Cardiovasc Imaging Rep. 2012 Feb;5(1):60-68
references.pmid: 22308200
references.citation: Nucl Med Biol. 2006 May;33(4):489-94
references.pmid: 16720240
references.citation: Science. 2010 Nov 19;330(6007):1066-71
references.pmid: 20929726
references.citation: Biotechnol Adv. 2011 Jan-Feb;29(1):142-55
references.pmid: 20959138
references.citation: Angew Chem Int Ed Engl. 2003 Jul 21;42(28):3251-3
references.pmid: 12876735
references.citation: Bioorg Med Chem Lett. 2010 Mar 15;20(6):1861-5
references.pmid: 20172716
references.citation: Chembiochem. 2011 Aug 16;12(12):1897-903
references.pmid: 21739561
references.citation: Curr Cancer Drug Targets. 2011 Feb;11(2):184-9
references.pmid: 21158723
references.citation: J Nucl Med. 2008 Jun;49(6):963-9
references.pmid: 18483105
references.citation: Nat Nanotechnol. 2008 Mar;3(3):145-50
references.pmid: 18654486
references.citation: Am J Pathol. 2009 Feb;174(2):602-12
references.pmid: 19147814
references.citation: Chembiochem. 2008 May 5;9(7):1154-8
references.pmid: 18412193
references.citation: Mol Imaging Biol. 2009 Jan-Feb;11(1):31-8
references.pmid: 18773246
references.citation: J Surg Res. 2009 Aug;155(2):231-6
references.pmid: 19482312
references.citation: Chem Soc Rev. 2012 Apr 7;41(7):2539-44
references.pmid: 22310807
references.citation: Mol Imaging Biol. 2012 Feb;14(1):106-14
references.pmid: 21347799
references.citation: J Nucl Med. 2010 Nov;51(11):1796-804
references.pmid: 20956475
references.citation: Chem Soc Rev. 2012 Aug 7;41(15):5239-61
references.pmid: 22743644
references.citation: Nat Med. 2006 Jun;12(6):657-64
references.pmid: 16715089
references.citation: Biomaterials. 2010 Jun;31(18):4995-5006
references.pmid: 20347138
references.citation: J Med Chem. 2011 Nov 10;54(21):7648-62
references.pmid: 21905730
references.citation: J Cereb Blood Flow Metab. 2002 Aug;22(8):899-907
references.pmid: 12172375
references.citation: Biochem Biophys Res Commun. 2011 Apr 15;407(3):525-30
references.pmid: 21414299
references.citation: Chembiochem. 2011 Nov 25;12(17):2692-8
references.pmid: 21998043
references.citation: Nat Protoc. 2006;1(1):73-9
references.pmid: 17406214
references.citation: Anal Biochem. 2001 Oct 15;297(2):128-36
references.pmid: 11673879
references.citation: FASEB J. 2004 Aug;18(11):1240-2
references.pmid: 15180966
references.citation: J Nucl Med. 2011 Nov;52(11):1803-10
references.pmid: 22045709
references.citation: Magn Reson Imaging. 2008 Nov;26(9):1273-8
references.pmid: 18440173