Tumor targeting polymeric micelles loaded with ultrasmall superparamagnetic iron oxide

Xu Qilan; Ruan renxu; Hong Guobin

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Tumor targeting polymeric micelles loaded with ultrasmall superparamagnetic iron oxide

Xu Qilan 1,Ruan renxu 2,Hong Guobin 1 * #

1.Department of Radiology,The fifth affiliated hospital,Sun yat-sen university, ZhuHai, GuangDong 519000

2.School of Chemistry & Chemical Engineering，Sun Yat-Sen University，Guangzhou 510275

*Correspondence author

#Submitted by

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Funding: New Teacher Fund for Doctor Station, the Ministry of Education（No.No. 20090171120091）

Opened online:10 September 2012

Accepted by: none

Citation: Xu Qilan,Ruan renxu,Hong Guobin.Tumor targeting polymeric micelles loaded with ultrasmall superparamagnetic iron oxide[OL]. [10 September 2012] http://en.paper.edu.cn/en_releasepaper/content/4488376

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 SPIONs encapsulation with PEG-PCL micelles (PEG-PCL-SPIONs) simultaneously increases transversal (r2) and decreases longitudinal (r1) magnetic resonance (MR) relaxivities of water proton in micelle solution, leading to a notably high r2/r1 ratio up to 78, which makes the PEG-PCL-SPIONs a highly sensitive MRI T2 contrast agent. The mean size of folate attached SPION micelles (Fa-PEG-PCL-SPIONs) is 44 ? 3nm 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 3h after intravenous injection of the Fa-PEG-PCL-SPIONs solution into mice bearing subcutaneous xenografts of human Bel 7402 hepatoma , a 41.2% signal intensity decrease was detected in the T2-weighted MR images of the tumor, indicating the efficient accumulation of Fa-PEG-PCL-SPIONs in the tumor tissue.

Keywords:Tumor targeting; Magnetic resonance imaging; Polymeric micelles; Superparamagnetic iron oxide

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