title: Tumor cell targeting by iron oxide nanoparticles is dominated by different factors in vitro versus in vivo.
abstract: Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting. In vitro, molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation in vivo, where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the in vitro results, PEGylation did not influence in vivo IONP biodistribution. Thus, the results reported here indicate that the in vitro advantages of molecular targeting may not consistently extend to pre-clinical in vivo settings. These observations may have important implications for the design and clinical translation of advanced, multifunctional, IONP platforms.
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: NDong
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Tate
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Kett
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America.
authors.forename: Jaya
authors.initials: J
authors.lastname: Batra
authors.affiliation: Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America.
authors.forename: Eugene
authors.initials: E
authors.lastname: Demidenko
authors.affiliation: Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America.
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
authors.affiliation: Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America; Department of Biological Sciences, Dartmouth, Hanover, NH, United States of America; Department of Chemistry, Dartmouth, Hanover, NH, United States of America.
authors.forename: Tillman U
authors.initials: TU
authors.lastname: Gerngross
authors.affiliation: Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America; Program in Molecular and Cellular Biology, Dartmouth, Hanover, NH, United States of America; Department of Biological Sciences, Dartmouth, Hanover, NH, United States of America.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Griswold
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; C000499:ferric oxide; C508053:ERBB2 protein, human