cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors
cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors
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DOI：
10.1016/j.jconrel.2017.04.033
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发表时间：
2017-07-28
影响因子：
10.8
通讯作者：
Kataoka, K.
中科院分区：
文献类型：
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作者：
Quader, S.;Liu, X.;Kataoka, K.
目前针对多形性胶质母细胞瘤(GBM)的治疗策略都是徒劳的，这主要是因为药物难以进入恶性组织，而GBM血管系统中紧密的血-脑肿瘤屏障阻碍了这种治疗。纳米药物已显示出绕过GBM的血管屏障的潜力，特别是通过靶向GBM血管内皮细胞管腔一侧的标志物来实现有效和选择性的移位到肿瘤中。因此，由于GBM内皮细胞过度表达的αvβ3和αvβ5整合素可以被环状精氨酸-甘氨酸-天冬氨酸(CRGD)多肽靶向，因此，我们开发了cRGD胶束纳米药物，通过pH敏感的糖键负载高效的抗胶质母细胞瘤药物表阿霉素，用于有效治疗GBM。这些安装了cRGD的表柔比星聚合物胶束(cRGD-Epi/m)比没有cRGD的胶束更快、更高地渗透到U87 MG细胞衍生的3D球体中，这可能是通过cRGD-整合素介导的途径实现的。在体内，cRGD安装的胶束通过在肿瘤组织中传递高水平的表阿霉素，有效地抑制了原位GBM模型的生长。这些结果表明，cRGD-Epi/m作为一种有效的、可翻译的治疗GBM的方法具有重要的前景。
Current therapeutic strategies against glioblastoma multiforme (GBM) are futile mainly because of the poor access of drugs into malignant tissues, which is hindered by the tight blood-brain tumor barrier in the GBM vasculature. Nanomedicines have shown potential for circumventing the vascular barriers of GBM, particularly by targeting markers on the luminal side of endothelial cells in the blood vessels of GBM for achieving effective and selective translocation into the tumor. Thus, as the alpha v beta 3 and alpha v beta 5 integrins overexpressed on the endothelial cells of GBM can be targeted by cyclic-Arg-Gly-Asp (cRGD) peptide, herein, we developed cRGDinstalled micellar nanomedicines loading epirubicin, the potent antiglioblastoma agent, through a pH-sensitive hydrazone-bond for effective treatment of GBM. These cRGD-installed epirubicin-loaded polymeric micelles (cRGD-Epi/m) achieved faster and higher penetration into U87MG cell-derived 3D-spheroids than the micelles without cRGD, conceivably through a cRGD-integrin mediated pathway. In vivo, the cRGD-installed micelles effectively suppressed the growth of an orthotopic GBM model by delivering high levels of epirubicin throughout the tumor tissue. These results indicate significant prospects for cRGD-Epi/m as an effective and translationable treatment against GBM.