title: Image-guided local delivery strategies enhance therapeutic nanoparticle uptake in solid tumors.
abstract: Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome many of the limitations of current cancer chemotherapeutics. However, a major challenge to many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical adoption of NP therapeutics. To overcome these limitations, we have adapted the techniques of image-guided local drug delivery to develop nanoablation and nanoembolization. Nanoablation is a tumor ablative strategy that employs image-guided placement of electrodes into tumor tissue to electroporate tumor cells, resulting in a rapid influx of NPs that is not dependent on cellular uptake machinery or stage of the cell cycle. Nanoembolization involves the image-guided delivery of NPs and embolic agents directly into the blood supply of tumors. We describe the design and testing of our innovative local delivery strategies using doxorubicin-functionalized superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We demonstrate that local delivery techniques result in significantly increased intratumoral DOX-SPIO uptake, with limited off-target delivery in tumor-bearing animal models. The techniques described are versatile enough to be extended to any NP platform, targeting any solid organ malignancy that can be accessed via imaging guidance.
authors: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center , Chicago Illinois 60611, United States.
authors: Samdeep K
authors: SK
authors: Mouli
authors: Patrick
authors: P
authors: Tyler
authors: Joseph L
authors: JL
authors: McDevitt
authors: Aaron C
authors: AC
authors: Eifler
authors: Yang
authors: Y
authors: Guo
authors: Jodi
authors: J
authors: Nicolai
authors: Robert J
authors: RJ
authors: Lewandowski
authors: Weiguo
authors: W
authors: Li
authors: Daniel
authors: D
authors: Procissi
authors: Robert K
authors: RK
authors: Ryu
authors: Y Andrew
authors: YA
authors: Wang
authors: Riad
authors: R
authors: Salem
authors: Andrew C
authors: AC
authors: Larson
authors: Reed A
authors: RA
authors: Omary
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004621:Embolization, Therapeutic / Q000379:methods*; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D004317:Doxorubicin
references: Magn Reson Med. 2008 Oct;60(4):970-5
references: 18816818
references: J Vasc Interv Radiol. 2009 Jul;20(7 Suppl):S317-23
references: 19560017
references: Cancer Res. 2010 Feb 15;70(4):1555-63
references: 20124486
references: Cell. 2011 Oct 14;147(2):275-92
references: 22000009
references: J Magn Reson Imaging. 2006 Oct;24(4):939-44
references: 16958064
references: Br J Radiol. 2006 Sep;79 Spec No 1:S2-15
references: 16980682
references: ACS Nano. 2010 Oct 26;4(10):5887-96
references: 20863096
references: Cancer Res. 2006 Jul 1;66(13):6732-40
references: 16818648
references: Radiology. 2003 Jan;226(1):214-20
references: 12511693
references: Adv Drug Deliv Rev. 2008 Aug 17;60(11):1252-65
references: 18558452
references: Int J Nanomedicine. 2008;3(3):311-21
references: 18990940
references: Eur J Cancer. 2006 May;42(8):1031-9
references: 16616487
references: Cancer Res. 1993 Nov 15;53(22):5462-9
references: 7693342
references: Invest Radiol. 2006 Apr;41(4):410-4
references: 16523024
references: J Natl Cancer Inst. 1988 Nov 16;80(18):1445-50
references: 3054127
references: Lab Anim. 2005 Jul;39(3):314-20
references: 16004691
references: Nat Rev Cancer. 2006 Aug;6(8):583-92
references: 16862189
references: J Vasc Interv Radiol. 2012 Mar;23(3):385-95
references: 22265247
references: Radiology. 2010 Dec;257(3):624-40
references: 21084414
references: Biomaterials. 2010 Jul;31(20):5397-407
references: 20398933
references: Adv Drug Deliv Rev. 2011 Mar 18;63(3):136-51
references: 20441782
references: Nanomedicine (Lond). 2010 Jun;5(4):523-8
references: 20528447
references: Chem Commun (Camb). 2004 Oct 21;(20):2306-7
references: 15489993
references: J Natl Cancer Inst. 2006 Mar 1;98(5):335-44
references: 16507830
references: Adv Drug Deliv Rev. 2011 Mar 18;63(3):131-5
references: 20304019
references: Am J Clin Oncol. 2012 Apr;35(2):167-77
references: 21127414
references: Methods Mol Biol. 2008;423:91-107
references: 18370192
references: Hepatology. 2002 May;35(5):1164-71
references: 11981766
references: Radiology. 2010 Aug;256(2):424-32
references: 20656834
references: Radiology. 2007 Oct;245(1):130-9
references: 17885186
references: Phys Med Biol. 2009 Sep 7;54(17):5109-21
references: 19661569
references: J Vasc Interv Radiol. 2008 Oct;19(10):1483-9
references: 18922400
references: Nat Rev Drug Discov. 2008 Sep;7(9):771-82
references: 18758474
references: Am J Transl Res. 2010 Nov 01;3(1):114-20
references: 21139811
references: ACS Nano. 2012 Jun 26;6(6):4694-701
references: 22607191
references: J Vasc Interv Radiol. 2012 Feb;23(2):265-73
references: 22178040
references: J Vasc Interv Radiol. 2008 Jun;19(6):931-6
references: 18503910
references: Expert Rev Neurother. 2008 Oct;8(10):1507-25
references: 18928344
references: J Vasc Interv Radiol. 2000 Nov-Dec;11(10):1245-55
references: 11099235
references: Mol Pharm. 2008 Mar-Apr;5(2):316-27
references: 18217714
references: Am J Transplant. 2009 Aug;9(8):1920-8
references: 19552767
references: J Vasc Interv Radiol. 2007 Mar;18(3):411-8
references: 17377188
references: Adv Drug Deliv Rev. 2011 Jul 18;63(8):623-39
references: 21144874
references: Lancet. 2002 May 18;359(9319):1734-9
references: 12049862
references: Mol Pharm. 2005 May-Jun;2(3):194-205
references: 15934780
references: Magn Reson Med. 1994 Dec;32(6):749-63
references: 7869897
references: Nat Rev Clin Oncol. 2010 Nov;7(11):653-64
references: 20838415
references: J Magn Reson Imaging. 2008 May;27(5):1069-76
references: 18407540
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15549-54
references: 17875985
references: Nat Rev Drug Discov. 2009 Oct;8(10):806-23
references: 19794444
references: Exp Cell Res. 1995 Apr;217(2):506-16
references: 7535239
references: Methods Mol Med. 2000;37:99-117
references: 21445731
references: Radiology. 2008 Dec;249(3):845-54
references: 18840788
references: J Vasc Interv Radiol. 2007 May;18(5):639-45
references: 17494846
references: Magn Reson Med. 2002 Jul;48(1):52-61
references: 12111931
references: Gastroenterology. 2009 May;136(5):1514-25.e2
references: 19208341
references: J Magn Reson Imaging. 2006 Jul;24(1):242-7
references: 16758469
references: J Biomed Nanotechnol. 2008 Dec 1;4(4):439-449
references: 25152701
references: Magn Reson Med. 2005 Oct;54(4):769-74
references: 16161115
references: Biomaterials. 2011 Jun;32(16):3988-99
references: 21392823