title: Induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics.
abstract: OBJECTIVE
  Combined therapeutic and diagnostic agents, "theranostics" are emerging valuable tools for noninvasive imaging and drug delivery. Here, we report on a solid biodegradable multifunctional nanoparticle that combines both features.
  
  
  METHODS
  Poly(lactide-co-glycolide) nanoparticles were engineered to confine superparamagnetic iron oxide contrast for magnetic resonance imaging while enabling controlled drug delivery and targeting to specific cells. To achieve this dual modality, fatty acids were used as anchors for surface ligands and for encapsulated iron oxide in the polymer matrix.
  
  
  RESULTS
  We demonstrate that fatty acid modified iron oxide prolonged retention of the contrast agent in the polymer matrix during degradative release of drug. Antibody-fatty acid surface modification facilitated cellular targeting and subsequent internalization in cells while inducing clustering of encapsulated fatty-acid modified superparamagnetic iron oxide during particle formulation. This induced clustered confinement led to an aggregation within the nanoparticle and, hence, higher transverse relaxivity, r2 , (294 mM(-1) s(-1) ) compared with nanoparticles without fatty-acid ligands (160 mM(-1) s(-1) ) and higher than commercially available superparamagnetic iron oxide nanoparticles (89 mM(-1) s(-1) ).
  
  
  CONCLUSIONS
  Clustering of superparamagnetic iron oxide in poly(lactide-co-glycolide) did not affect the controlled release of encapsulated drugs such as methotrexate or clodronate and their subsequent pharmacological activity, thus highlighting the full theranostic capability of our system.
authors: Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
authors: Ragy R T
authors: RR
authors: Ragheb
authors: Dongin
authors: D
authors: Kim
authors: Arunima
authors: A
authors: Bandyopadhyay
authors: Halima
authors: H
authors: Chahboune
authors: Beyza
authors: B
authors: Bulutoglu
authors: Harib
authors: H
authors: Ezaldein
authors: Jason M
authors: JM
authors: Criscione
authors: Tarek M
authors: TM
authors: Fahmy
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002478:Cells, Cultured; D003911:Dextrans / Q000737:chemistry* / Q000627:therapeutic use; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D008264:Macrophages / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D008422:Materials Testing; D008546:Melanoma, Experimental / Q000737:chemistry* / Q000175:diagnosis / Q000628:therapy; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; C097921:ferumoxtran-10
keywords: PLGA; clodronate; clustered; iron oxide; methotrexate; targeted
references: Bioconjug Chem. 2011 Oct 19;22(10):1879-903
references: 21830812
references: Radiology. 2001 Feb;218(2):570-5
references: 11161180
references: Biomaterials. 2009 Dec;30(36):6947-54
references: 19783295
references: J Control Release. 2011 Nov 30;156(1):109-15
references: 21723893
references: Biomaterials. 2008 Apr;29(10):1473-83
references: 18155133
references: Nano Lett. 2006 Nov;6(11):2427-30
references: 17090068
references: J Am Chem Soc. 2002 Jul 17;124(28):8204-5
references: 12105897
references: Magn Reson Med. 2011 Jun;65(6):1776-85
references: 21404328
references: Adv Drug Deliv Rev. 2006 Dec 1;58(14):1471-504
references: 17116343
references: Biomaterials. 2010 May;31(13):3502-11
references: 20144844
references: Adv Drug Deliv Rev. 2008 Aug 17;60(11):1241-51
references: 18508157
references: J Cereb Blood Flow Metab. 2010 Jan;30(1):15-35
references: 19756021
references: Mol Pharm. 2011 Apr 4;8(2):520-31
references: 21381651
references: Biomaterials. 2010 Apr;31(12):3296-306
references: 20116846
references: Theranostics. 2012;2:122-4
references: 22287992
references: J Magn Reson Imaging. 2007 Dec;26(6):1634-41
references: 17968941
references: Biomaterials. 2005 Oct;26(28):5727-36
references: 15878378
references: J Am Chem Soc. 2004 Jan 14;126(1):273-9
references: 14709092
references: Angew Chem Int Ed Engl. 2009;48(2):321-4
references: 19040234
references: J Am Chem Soc. 2008 Jul 23;130(29):9186-7
references: 18572935
references: Nanotechnology. 2011 Aug 12;22(32):325702
references: 21772073
references: Nano Lett. 2012 Aug 8;12(8):4131-9
references: 22769232
references: Blood. 2003 Jan 15;101(2):594-601
references: 12393630
references: Int J Lab Hematol. 2008 Jun;30(3):185-90
references: 18479295
references: Nano Lett. 2008 Dec;8(12):4116-21
references: 19367878
references: Biomaterials. 2005 May;26(15):2713-22
references: 15585275
references: Annu Rev Immunol. 1999;17:593-623
references: 10358769
references: Radiology. 2006 May;239(2):481-7
references: 16641354
references: IEEE Trans Nanobioscience. 2004 Mar;3(1):66-73
references: 15382647
references: Mol Pharm. 2010 Feb 1;7(1):32-40
references: 19708690
references: Acad Radiol. 2002 Feb;9(2):198-202
references: 11918373
references: Small. 2010 Feb 5;6(3):366-70
references: 20020469
references: Small. 2008 Oct;4(10):1640-5
references: 18819168