Folate-conjugated cross-linked magnetic nanoparticles as potential magnetic resonance probes for in vivo cancer imaging
JOURNAL OF MATERIALS CHEMISTRY B(2013)
摘要
Superparamagnetic iron oxide nanoparticles are widely used as nanoprobes for magnetic resonance imaging (MRI). In this study, a novel type of cross-linked magnetic nanoparticle was developed in an effort to improve the structural stability of amphiphilic polymer-coated iron oxide nanoparticles. Iron oxide nanocrystals were coated with a cross-linkable amphiphilic graft copolymer, poly(succinimide) grafted with folate-conjugated polyethylene glycol (PEG) and alkyl chains. The tumor-specific targeting ligand, folate, was included to target and detect cancer cells. The hydrophobic portions of the amphiphilic copolymer on the surfaces of the nanoparticles were cross-linked via an aminolysis reaction between the succinimide units and a bifunctional primary amine. The folate-conjugated cross-linked magnetic nanoparticles (F-CLMNPs) were 40 nm in diameter and displayed a low cytotoxicity, even at relatively high concentrations. The F-CLMNPs exhibited highly efficient intracellular uptake into KB cells, which overexpress the folate receptor, as determined by fluorescence microscopy, flow cytometry, and Prussian blue staining. In vivo MR images of a mouse bearing a KB cell tumor displayed a 75% drop in the T2 signal in the tumor tissues within 3 hours. These results indicated that the F-CLMNPs accumulated at the tumor site and were highly effective for tumor detection using in vivo MRI techniques.
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