Potentiating Chemotherapy Efficacy in Neuroblastoma Cells via Disialoganglioside2 Targeting Mixed Micelles
Potentiating Chemotherapy Efficacy in Neuroblastoma Cells via Disialoganglioside2 Targeting Mixed Micelles
复制标题
通过靶向混合胶束的双唾液酸神经节苷脂 2 增强神经母细胞瘤细胞的化疗效果
DOI：
10.1166/jnn.2016.12964
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发表时间：
2016-12
影响因子：
--
通讯作者：
Jian Wang
中科院分区：
文献类型：
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作者：
He Zhao;Mei-Fang Jing;Zhi-Heng Li;Jian Pan;Wei Li;Jian Wang
化疗在神经母细胞瘤（NB）的治疗中占有重要地位，但其特异性较差。胶束与抗体的结合为实体瘤靶向化疗提供了新的途径。因此，我们精细地合成并制备了基于维生素E D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）和聚（N-异丙基丙烯酰胺-co-N，N-二甲基丙烯酰胺）118-聚（D，L-乳酸-co-乙醇酸）71（PID 118-b-PLA 71）的抗二唾液酸神经节苷脂2抗体修饰的混合胶束，其可以靶向GD 2并响应于温度刺激。实验结果表明，以二唾液酸神经节苷脂2（GD 2）为靶向的混合胶束的体积相变温度（VPTT）约为40 °C。当T > VPTT时，GD 2靶向混合胶束的平均粒径从150 nm增加到500 nm左右，药物释放更加完全。GD 2导航的混合胶束对阿霉素（DOX）的细胞摄取约为Doxil的3倍。对GD 2 + NB细胞的细胞毒性试验表明，在相同条件下，DOX负载的GD 2靶向混合胶束的半数最大抑制浓度（IC 50）是Doxil的四分之一。细胞凋亡研究表明，DOX-GD 2靶向混合胶束诱导的细胞凋亡率约为Doxil的3倍。GD 2靶向混合胶束具有良好的球形结构和高稳定性，显著增强了阿霉素在NB细胞中的抗癌活性。
Chemotherapy plays an important role in treatment of neuroblastoma (NB), however, it has poor specificity. Combination of micelle and antibody provides a new way for targeting chemotherapy in solid tumors nowadays. We therefore finely synthesized and fabricated anti-Disialoganglioside2 antibody decorated mixed micelles, based on vitamin E D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (N-isopropylacrylamide-co-N,N-dimethylacrylamide)118-poly(D, L-lactic-co-glycolic acid)71 (PID118-b-PLA71), which can target GD2 and respond to temperature stimulation. The experimental results demonstrated that the volume phase transition temperature (VPTT) for the Disialoganglioside2 (GD2) targeting mixed micelles was about 40 °C. At T > VPTT, the GD2 targeting mixed micelles exhibited a more complete drug release, with mean diameter increasing from 150 nm to 500 nm approximately. The cellular uptake of doxorubicin (DOX) by the GD2-navigated mixed micelles was about three times that of Doxil. Cytotoxicity assays against the GD2+ NB cells showed that the half maximal inhibitory concentration (IC50) of the DOX-loaded GD2 targeting mixed micelles was one fourth that of Doxil at the same conditions. Cell apoptosis studies showed that cell apoptosis rate induced by the DOX-loaded GD2 targeting mixed micelles was about three times that of Doxil. With fine and spherical structure, and also high stability, the GD2 targeting mixed micelles significantly enhanced the DOX anticancer activity in the NB cells.