Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles

• DOI: 10.1021/acs.molpharmaceut.6b00523
• Publication Date: 2016-09-16T19:18:32Z
• Authors: Lingyan Lv; Yan Jiang; Xin Liu; Baoyan Wang; Wei Lv; Yue Zhao; Huihui Shi; Quanyin Hu; Hongliang Xin; Qunwei Xu; Zhen Gu
• Keywords: Male; Mice, Inbred BALB C; 0303 health sciences; Paclitaxel; Polyesters; Mice, Nude; Glioma; Antineoplastic Agents, Phytogenic; Polyethylene Glycols; Rats; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; Cell Line, Tumor; Human Umbilical Vein Endothelial Cells; Animals; Humans; Nanoparticles; Glioblastoma

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 Interleukin 13 receptor α2 (IL-13Rα2) on glioma heparan sulfate neovascular endothelial cells, we developed paclitaxel (PTX) loaded Pep-1 CGKRK peptide-modified PEG–PLGA nanoparticle (PC-NP-PTX) neovasculature dual-targeted chemotherapy enhance antiglioma efficacy. There were significant differences both enhancement cellular uptake in HUVEC C6 improvement vitro activity respect proliferation, tumor spheroid growth, tube formation, migration between PC-NP-PTX Taxol NP-PTX. As IC50 3.59 ± 0.056, 2.37 0.044, 1.38 0.028, 1.82 0.035, 1.00 0.016 μg/mL Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, PC-NP-PTX, 0.44 0.006, 0.33 0.005, 0.25 0.19 0.004, 0.16 0.004 respectively. vivo distribution assays confirmed that accumulated effectively at site. showed longer median survival time 61 days when compared with (22 days), NP-PTX (24 Pep-NP-PTX (32 CGKRK-NP-PTX (34 days). The efficacy safety evaluation significantly enhanced displayed negligible acute toxicity.