title: Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment.
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.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Ren
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhu
authors.forename: Fengyi
authors.initials: F
authors.lastname: Du
authors.forename: Chunlai
authors.initials: C
authors.lastname: Feng
authors.forename: Yike
authors.initials: Y
authors.lastname: Xie
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000008:administration & dosage* / Q000627:therapeutic use; D004146:Dioxanes / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004705:Endocytosis; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011108:Polymers / Q000008:administration & dosage* / Q000627:therapeutic use; D013347:Subcellular Fractions
chemical_list: D004146:Dioxanes; D011108:Polymers; C059299:polytrimethylene carbonate; D011092:Polyethylene Glycols; D003847:Deoxyglucose
keywords: Avascular glioma spheroids; Dual-targeted drug delivery system; Endocytic mechanism; Glioma; Glucose transporter