JOURNAL ARTICLE

Folate-targeted polymeric micelles loaded with ultrasmall superparamagnetic iron oxide: combined small size and high MRI sensitivity

Guo-bin Hong, Jing-xing Zhou, Ren-xu Yuan
International Journal of Nanomedicine 2012, 7: 2863-72
22745549
Targeted delivery of contrast agents is a highly desirable strategy for enhancing diagnostic efficiency and reducing side effects and toxicity. Water-soluble and tumor-targeting superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by loading hydrophobic SPIONs into micelles assembled from an amphiphilic block copolymer poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) bearing folate in the distal ends of PEG chains. Compared to the water-soluble SPIONs obtained by small molecular surfactant coating, ultrasmall SPION encapsulation with PEG-PCL micelles (PEG-PCL-SPIONs) simultaneously increases transverse (r(2)) and decreases longitudinal (r(1)) magnetic resonance (MR) relaxivities of water proton in micelle solution, leading to a notably high r(2)/r(1) ratio up to 78, which makes the PEG-PCL-SPIONs a highly sensitive MR imaging (MRI) T(2) contrast agent. The mean size of folate-attached SPION micelles (Fa-PEG-PCL-SPIONs) is 44 ± 3 nm on average, ideal for in vivo MRI applications in which long circulation is greatly determined by small particle size and is highly desirable. Prussian blue staining of BEL-7402 cells over-expressing folate receptors, after incubation with micelle-containing medium, demonstrated that folate functionalization of the magnetic particles significantly enhanced their cell uptake. The potential of Fa-PEG-PCL-SPIONs as a potent MRI probe for in vivo tumor detection was assessed. At 3 hours after intravenous injection of the Fa-PEG-PCL-SPION solution into mice bearing subcutaneous xenografts of human BEL-7402 hepatoma, a 41.2% signal intensity decrease was detected in the T(2)-weighted MR images of the tumor, indicating the efficient accumulation of Fa-PEG-PCL-SPIONs in the tumor tissue.

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