title: Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery.
abstract: OBJECTIVE
  Targeted delivery is a highly desirable strategy for diagnostic imaging because of enhanced efficacy and reduced dosage/toxicity. Receptor-targeting was used to deliver contrast-producing superparamagnetic iron oxide (IO) nanoparticle to receptor-expressing tumors for in vivo magnetic resonance (MR) imaging.
  
  
  METHODS
  Nanometer-sized, dextran-coated (maghemite) IO particles were prepared by a precipitation method. They were tethered with N-hydroxysuccinimide-folate and fluorescence isothiocyanate (FITC). For in vitro study of delivery specificity and efficiency, KB cells, a human nasopharyngeal epidermal carcinoma cell line expressing surface receptors for folic acid, were used as positive targets, and A549 cells, a human lung carcinoma cell line which lacks folate receptors, were used as negative control targets. In vivo MR images were obtained using mouse models with subcutaneous tumor xenografts grown from implanted KB cells.
  
  
  RESULTS
  Internalization of nanoparticles into targeted cells only occurred when IO was conjugated to folate and when the folate receptors are available and accessible on the cells. The endocytosis was efficient and rapid, as 97.5% KB cells cultured with folate-FITC-IO showed FITC uptake after 1 hour of incubation. In in vivo MR imaging, an average intensity decrease of 38% was observed from precontrast to postcontrast images of the tumor, which was about three times the intensity decrease observed at a non-tumor-bearing muscle.
  
  
  CONCLUSIONS
  Successful in vivo MR imaging of folate receptor-expressing tumors targeted by IO nanoparticles was demonstrated for the first time.
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, 3231 Walnut St, Philadelphia, PA 19104, USA.
authors.forename: Hoon
authors.initials: H
authors.lastname: Choi
authors.forename: Seok Rye
authors.initials: SR
authors.lastname: Choi
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chen
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage / Q000378:metabolism*; D003911:Dextrans / Q000494:pharmacology; D004195:Disease Models, Animal; D004705:Endocytosis / Q000187:drug effects; D005290:Ferric Compounds / Q000008:administration & dosage / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D009303:Nasopharyngeal Neoplasms / Q000000981:diagnostic imaging*; D010952:Plasma Substitutes / Q000494:pharmacology; D011856:Radiographic Image Enhancement; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity; D014018:Tissue Distribution / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058973:Folate Receptors, GPI-Anchored; D010952:Plasma Substitutes; D011956:Receptors, Cell Surface; C000499:ferric oxide; D005492:Folic Acid