title: Folate-targeted polymeric micelles loaded with ultrasmall superparamagnetic iron oxide: combined small size and high MRI sensitivity.
abstract: 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.
authors: Department of Radiology, Fifth Affiliated Hospital, Zhuhai, China.
authors: Guo-bin
authors: GB
authors: Hong
authors: Jing-xing
authors: JX
authors: Zhou
authors: Ren-xu
authors: RX
authors: Yuan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D005026:Ethylene Glycols; D058185:Magnetite Nanoparticles; D008823:Micelles; D011091:Polyesters; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D005492:Folic Acid