Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles
Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles
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双靶向纳米颗粒增强新血管系统和神经胶质瘤细胞的抗胶质母细胞瘤功效
DOI：
10.1021/acs.molpharmaceut.6b00523
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发表时间：
2016-10-01
影响因子：
4.9
通讯作者：
Gu, Zhen
中科院分区：
文献类型：
--
作者：
Lv, Lingyan;Jiang, Yan;Gu, Zhen
抗癌细胞和抗血管生成联合治疗被认为是治疗脑胶质母细胞瘤的一种潜在的靶向策略。本研究利用白细胞介素13受体α 2 （IL-13R α 2）在胶质瘤细胞上的过表达和硫酸肝素在新生血管内皮细胞上的过表达，开发了一种载Pep-1和CGKRK肽修饰PEGPLGA的紫杉醇（PTX）纳米颗粒（PC-NP-PTX），用于胶质瘤细胞和新生血管双靶向化疗，以提高抗胶质瘤的疗效。PC-NP-PTX与紫杉醇和NP-PTX在增强HUVEC和C6细胞的细胞摄取和提高体外抗胶质瘤活性方面均有显著差异，在增殖、肿瘤球生长、管形成和迁移方面均有显著差异。C6细胞对紫杉醇、NP-PTX、Pep-NP-PTX、CGKRK-NP-PTX、PC-NP-PTX的IC50分别为3.59 +/- 0.056、2.37 +/- 0.044、1.38 +/- 0.028、1.82 +/- 0.035、1.00 +/- 0.016 μ g/mL， HUVEC细胞对紫杉醇、NP-PTX、Pep-NP-PTX、CGKRK-NP-PTX、PC-NP-PTX的IC50分别为0.44 +/- 0.006、0.33 +/- 0.005、0.25 +/- 0.005、0.19 +/- 0.004、0.16 +/- 0.004 μ g/mL。体内分布试验证实PC-NP-PTX能有效靶向并在胶质瘤部位积累。与紫杉醇（22天）、NP-PTX（24天）、Pep-NP-PTX（32天）和CGKRK-NP-PTX（34天）相比，PC-NP-PTX的中位生存时间更长，为61天。体内抗胶质瘤疗效和安全性评价显示，PC-NP-PTX可显著增强抗胶质瘤疗效，急性毒性可忽略不计。
Combining treatment of anticancer cells and antiangio-genesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor alpha 2 (IL-13R alpha 2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEGPLGA 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 IC50 were 3.59 +/- 0.056, 2.37 +/- 0.044, 1.38 +/- 0.028, 1.82 +/- 0.035, and 1.00 +/- 0.016 mu g/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50 were 0.44 +/- 0.006, 0.33 +/- 0.005, 0.25 +/- 0.005, 0.19 +/- 0.004, and 0.16 +/- 0.004 mu g/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.