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  • Title: Folate-functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs.
    Author: Hong G, Yuan R, Liang B, Shen J, Yang X, Shuai X.
    Journal: Biomed Microdevices; 2008 Oct; 10(5):693-700. PubMed ID: 18350380.
    Abstract:
    Targeted delivery is a highly desirable strategy to improve the diagnostic imaging and therapeutic outcome because of enhanced efficacy and reduced toxicity. In the current research, anticancer drug doxorubicin (DOX) and contrast agent for magnetic resonance imaging (MRI), herein superparamagnetic ion oxide Fe(3)O(4) (SPIO), were accommodated in the core of micelles self-assembled from amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) with a targeting ligand (folate) attached to the distal ends of PEG (Folate-PEG-PCL). The in vitro tumor cell targeting efficacy of these folate functionalized and DOX/SPIO-loaded micelles (Folate-SPIO-DOX-Micelles) was evaluated upon observing cellular uptake of micelles by human hepatic carcinoma cells (Bel 7402 cells) which overexpresses surface receptors for folic acid. In the Prussian blue staining experiments, cells incubated with Folate-SPIO-DOX-Micelles showed much higher intracellular iron density than the cells incubated with the folate-free SPIO-DOX-Micelles. According to the flow cytometry data, cellular DOX uptake observed for the folate targeting micelle was about 2.5 fold higher than that for the non-targeting group. Furthermore, MTT assay showed that Folate-SPIO-DOX-Micelles effectively inhibited cell proliferation, while the folate-free SPIO-DOX-Micelles did not show the same feat at comparable DOX concentrations. The potential of Folate-SPIO-DOX-Micelle as a novel MRI-visible nanomedicine platform was assessed with a 1.5 T clinical MRI scanner. The acquired MRI T (2) signal intensity of cells treated with the folate targeting micelles decreased significantly. By contrast, T (2) signal did not show obvious decrease for cells treated with the folate-free micelles. Our results indicate that the multifunctional polymeric micelles, Folate-SPIO-DOX-Micelles, have better targeting tropism to the hepatic carcinoma cells in vitro than their non-targeting counterparts, and the cell targeting events of micelles can be monitored using a clinical MRI scanner.
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