Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

Christian Ndong,1 Seiko Toraya-Brown,2 Katsiaryna Kekalo,1 Ian Baker,1 Tillman U Gerngross,1,3,4 Steven N Fiering,2,5,6 Karl E Griswold1,3,6 1Thayer School of Engineering, Dartmouth, Hanover, NH, USA; 2Department of Microbiology and Immunology, Geisel School of Medicine at Dartmo...

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Autores principales:	Ndong C, Toraya-Brown S, Kekalo K, Baker I, Gerngross TU, Fiering SN, Griswold KE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2375a28548b0405b8e50bd05f06d4e82
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spelling	oai:doaj.org-article:2375a28548b0405b8e50bd05f06d4e822021-12-02T05:10:42ZAntibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo1178-2013https://doaj.org/article/2375a28548b0405b8e50bd05f06d4e822015-04-01T00:00:00Zhttp://www.dovepress.com/antibody-mediated-targeting-of-iron-oxide-nanoparticles-to-the-folate--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Christian Ndong,1 Seiko Toraya-Brown,2 Katsiaryna Kekalo,1 Ian Baker,1 Tillman U Gerngross,1,3,4 Steven N Fiering,2,5,6 Karl E Griswold1,3,6 1Thayer School of Engineering, Dartmouth, Hanover, NH, USA; 2Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 3Department of Biological Sciences, Dartmouth, Hanover, NH, USA; 4Department of Chemistry, Dartmouth, Hanover, NH, USA; 5Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 6Norris Cotton Cancer Center, Lebanon, NH, USA Abstract: Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm nanoparticles exhibited lower in vitro targeting efficiency when compared to those built with commercially sourced 180 nm nanoparticles. In vivo, however, the two Ffab-IONP platforms achieved equivalent tumor homing, although the smaller 120 nm IONPs were more prone to liver sequestration. Overall, the results show that Ffab-mediated targeting of IONPs yields specific, high-level accumulation within cancer cells, and this fact suggests that Ffab-IONPs could have future utility in ovarian cancer diagnostics and therapy. Keywords: nanoparticle targeting, antibody fragment, biodistribution, ovarian cancerNdong CToraya-Brown SKekalo KBaker IGerngross TUFiering SNGriswold KEDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2595-2617 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ndong C Toraya-Brown S Kekalo K Baker I Gerngross TU Fiering SN Griswold KE Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
description	Christian Ndong,1 Seiko Toraya-Brown,2 Katsiaryna Kekalo,1 Ian Baker,1 Tillman U Gerngross,1,3,4 Steven N Fiering,2,5,6 Karl E Griswold1,3,6 1Thayer School of Engineering, Dartmouth, Hanover, NH, USA; 2Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 3Department of Biological Sciences, Dartmouth, Hanover, NH, USA; 4Department of Chemistry, Dartmouth, Hanover, NH, USA; 5Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 6Norris Cotton Cancer Center, Lebanon, NH, USA Abstract: Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm nanoparticles exhibited lower in vitro targeting efficiency when compared to those built with commercially sourced 180 nm nanoparticles. In vivo, however, the two Ffab-IONP platforms achieved equivalent tumor homing, although the smaller 120 nm IONPs were more prone to liver sequestration. Overall, the results show that Ffab-mediated targeting of IONPs yields specific, high-level accumulation within cancer cells, and this fact suggests that Ffab-IONPs could have future utility in ovarian cancer diagnostics and therapy. Keywords: nanoparticle targeting, antibody fragment, biodistribution, ovarian cancer
format	article
author	Ndong C Toraya-Brown S Kekalo K Baker I Gerngross TU Fiering SN Griswold KE
author_facet	Ndong C Toraya-Brown S Kekalo K Baker I Gerngross TU Fiering SN Griswold KE
author_sort	Ndong C
title	Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
title_short	Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
title_full	Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
title_fullStr	Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
title_full_unstemmed	Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
title_sort	antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/2375a28548b0405b8e50bd05f06d4e82
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Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

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