Targeted delivery of docetaxel via Pi-Pi stacking stabilized dendritic polymeric micelles for enhanced therapy of liver cancer
Targeted delivery of docetaxel via Pi-Pi stacking stabilized dendritic polymeric micelles for enhanced therapy of liver cancer
复制标题
通过 Pi-Pi 堆积稳定的树枝状聚合物胶束靶向递送多西紫杉醇，以增强肝癌的治疗
DOI：
10.1016/j.msec.2017.02.098
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发表时间：
2017-06-01
影响因子：
7.9
通讯作者：
Liang, Yong
中科院分区：
文献类型：
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作者：
Tang, Xiaolong;Zhou, Shuping;Liang, Yong
包括多西紫杉醇（DTX）在内的紫杉烷类化疗药物通过传统的聚合物胶束递送仍然存在稳定性不足和在循环过程中快速过早释放的问题，这限制了它们的靶向性和抗癌效率。为了克服这些挑战，我们开发了一种新的负载dtx的Pi-Pi堆叠稳定树突状聚合物胶束，用于肝癌的靶向治疗。由DTX和可生物降解的枝状嵌段共聚物聚（氨基胺）-聚（γ -苄基- l-谷氨酸）-b-聚乙二醇- crgd （PAM-PBLG-b-PEG-cRGD）自组装而成，称为DPM-DTX-cRGD。DPM-DTX-cRGD由于其共价树突状结构而具有很强的稳定性，并且可以通过DTX与PBLG片段的芳香基团之间的Pi-Pi堆叠加载大量的DTX，并具有良好的保留性。细胞摄取研究表明，与非靶向DPM相比，crgd共轭的树突状聚合物胶束（DPM）在人肝癌HepG2细胞中表现出更高的细胞摄取。MTT试验还证实，DPM-DTX- crgd比非靶向DPM-DTX和临床可用的DTX制剂（泰索帝）产生更大的细胞毒性。因此，这种DPM-DTX-cRGD为肝癌靶向治疗提供了一种新的有吸引力的方法。(C) 2017年Elsevier B.V.出版
Delivery of taxane-based chemotherapeutics including Docetaxel (DTX) by conventional polymeric micelles still suffers from insufficient stability and rapid premature release during the circulation, which limits their targeting and anticancer efficiency. To conquer these challenges, we developed a novel DTX-loaded Pi-Pi stacking stabilized dendritic polymeric micelle for targeted therapy of liver cancer. This dendritic polymeric micelle, referred to DPM-DTX-cRGD, was self-assembled from DTX and biodegradable dendritic block copolymers Poly(amidoamine)-poly(gamma-benzyl-L-Glutamate)-b-polyethylene glycol-cRGD (PAM-PBLG-b-PEG-cRGD). DPM-DTX-cRGD held robust stability due to its covalent dendritic structure and would load abundant DTX with excellent retention via Pi-Pi stacking between DTX and the aromatic groups of the PBLG segments. The cellular uptake studies demonstrated that the cRGD-conjugated dendritic polymeric micelle (DPM) exhibited much higher cellular uptake in human liver cancer HepG2 cells than non-targeted DPM. The MTT assay also confirmed that DPM-DTX-cRGD caused much greater cytotoxicity than non-targeted DPM-DTX and a clinically available DTX formulation (Taxotere). Therefore, this DPM-DTX-cRGD provides a novel attractive approach for targeted therapy of liver cancer. (C) 2017 Published by Elsevier B.V.