Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery.
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.
Choi
Hoon
H
Department of Materials Science and Engineering, University of Pennsylvania, 3231 Walnut St, Philadelphia, PA 19104, USA.
Choi
Seok Rye
SR
Zhou
Rong
R
Kung
Hank F
HF
Chen
I-Wei
IW
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
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