title: Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles.
abstract: Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG-PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of in vitro antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC50were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. In vivo distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The in vivo antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.|Department of Pharmacy, Zhangjiagang Hospital of Traditional Chinese Medicine, Affiliated Nanjing University of Chinese Medicine , Zhangjiagang 215600, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Quanyin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University , Raleigh, North Carolina 27695, United States.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.|Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000188:drug therapy*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: antineovasculature; drug delivery; dual-targeted nanoparticle; glioma; paclitaxel