title: Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo.
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.
authors: Thayer School of Engineering, Dartmouth, Hanover, NH, USA.
authors: Christian
authors: C
authors: Ndong
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors: Seiko
authors: S
authors: Toraya-Brown
authors: Thayer School of Engineering, Dartmouth, Hanover, NH, USA.
authors: Katsiaryna
authors: K
authors: Kekalo
authors: Thayer School of Engineering, Dartmouth, Hanover, NH, USA.
authors: Ian
authors: I
authors: Baker
authors: Thayer School of Engineering, Dartmouth, Hanover, NH, USA ; Department of Biological Sciences, Dartmouth, Hanover, NH, USA ; Department of Chemistry, Dartmouth, Hanover, NH, USA.
authors: Tillman U
authors: TU
authors: Gerngross
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA ; Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA ; Norris Cotton Cancer Center, Lebanon, NH, USA.
authors: Steven N
authors: SN
authors: Fiering
authors: Thayer School of Engineering, Dartmouth, Hanover, NH, USA ; Department of Biological Sciences, Dartmouth, Hanover, NH, USA ; Norris Cotton Cancer Center, Lebanon, NH, USA.
authors: Karl E
authors: KE
authors: Griswold
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D058975:Folate Receptor 1 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*
chemical_list: D000906:Antibodies; D058975:Folate Receptor 1; D058185:Magnetite Nanoparticles
keywords: antibody fragment; biodistribution; nanoparticle targeting; ovarian cancer