Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.
Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.
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IL-13Rα2介导的共聚物纳米颗粒加载了带有紫杉醇的共聚物纳米颗粒改善了抗胶质母细胞瘤的功效。
DOI：
10.1038/srep16589
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发表时间：
2015-11-16
影响因子：
4.6
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Wang B;Lv L;Wang Z;Jiang Y;Lv W;Liu X;Wang Z;Zhao Y;Xin H;Xu Q
胶质瘤是恶性程度最高的脑肿瘤之一，由于脑肿瘤屏障的存在，治疗效果往往受到限制。基于白细胞介素13受体α2（IL-13 R α2）在胶质瘤细胞上的高表达，IL-13 R α2被证明是一种潜在的胶质瘤靶向受体。在本研究中，开发了Pep-1-缀合的聚乙二醇化紫杉醇纳米粒（Pep-NP-PTX）作为胶质瘤治疗的靶向药物递送系统。Pep-NP-PTX呈现令人满意的95.78 nm的尺寸，具有窄的尺寸分布。与NP-PTX相比，Pep-NP-PTX在C6细胞中表现出显著增强的细胞摄取（p < 0.001）。体外抗增殖实验表明，Pep-NP-PTX和NP-PTX的IC_（50）分别为146 ng/ml和349 ng/ml。体内荧光成像结果表明Pep-NP具有更高的特异性和效率。静脉注射Pep-NP-PTX后0.5、1和4 h可使PTX在胶质瘤切片中的分布增强，分别是NP-PTX组的1.98、1.91和1.53倍。Pep-NP-PTX可提高抗胶质瘤疗效，中位生存期为32天，明显长于PTX-NP（23天）和Taxol®（22天）。结论：Pep-NP-PTX是一种潜在的脑胶质瘤靶向给药系统。
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol® (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.