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  • Title: Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment.
    Author: Jiang X, Xin H, Ren Q, Gu J, Zhu L, Du F, Feng C, Xie Y, Sha X, Fang X.
    Journal: Biomaterials; 2014 Jan; 35(1):518-29. PubMed ID: 24125772.
    Abstract:
    Based on the facilitative glucose transporter (GLUT) over-expression on both blood-brain barrier (BBB) and glioma cells, 2-deoxy-d-glucose modified poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (dGlu-NP) were developed as a potential dual-targeted drug delivery system for enhancing the BBB penetration via GLUT-mediated transcytosis and improving the drug accumulation in the glioma via GLUT-mediated endocytosis. In vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of paclitaxel (PTX). Compared with non-glucosylated nanoparticles (NP), a significantly higher amount of dGlu-NP was internalized by RG-2 glioma cells through caveolae-mediated and clathrin-mediated endocytosis. Both of the transport ratios across the in vitro BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were significantly greater of dGlu-NP/PTX than that of NP/PTX. In vivo fluorescent image indicated that dGlu-NP had high specificity and efficiency in intracranial tumor accumulation. The anti-glioblastoma efficacy of dGlu-NP/PTX was significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary safety tests showed no acute toxicity to hematological system, liver, kidney, heart, lung and spleen in mice after intravenous administration at a dose of 100 mg/kg blank dGlu-NP per day for a week. Therefore, these results indicated that dGlu-NP developed in this study could be a potential dual-targeted vehicle for brain glioma therapy.
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