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COMPARATIVE STUDY
JOURNAL ARTICLE
Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery.
Academic Radiology 2004 September
RATIONALE AND 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.
MATERIALS AND 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.
CONCLUSION: Successful in vivo MR imaging of folate receptor-expressing tumors targeted by IO nanoparticles was demonstrated for the first time.
MATERIALS AND 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.
CONCLUSION: Successful in vivo MR imaging of folate receptor-expressing tumors targeted by IO nanoparticles was demonstrated for the first time.
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