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Development of functional dendrisomes based on a single molecule of polyesterbenzylether dendrimer and their application in cancer stem cell therapy
NPG Asia Materials ( IF 9.7 ) Pub Date : 2019-07-05 , DOI: 10.1038/s41427-019-0134-x
Li-Min Mu , Lei Liu , Rui Liu , Jia-Lun Duan , Shuang Ma , Xue-Qi Li , Yi-Nuo Cui , Zhan-Bo Su , Xiao Zhang , Jian-Xing Hu , Ying Xie , Ying Zheng , Wan-Liang Lu

The differentiation therapy of breast cancer stem cells (CSCs) represents a significant strategy to treat cancer, but inefficient delivery to CSCs hinders the efficacy of differentiation agents. In this work, we report a type of functional dendrisomes constructed by the synthesized amphiphilic dendrimers, which enhance cellular uptake by breast CSCs, differentiate breast CSCs by carrying all-trans retinoic acid (ATRA), and increase the anticancer efficacy by carrying ATRA and docetaxel (DTX) in vitro and in breast cancer-bearing mice. The study further reveals the mechanism of cellular uptake by breast CSCs and uncovers the differentiation mechanism by analyzing relevant signal molecules, transcription factors, and cell cycle-associated signaling pathways during differentiation therapy in breast CSCs. Hence, this study offers a novel type of functional dendrisomes for differentiation therapy of breast CSCs and has significant clinical implications.



中文翻译:

基于单分子聚酯苄基醚树枝状大分子的功能树突体的开发及其在癌症干细胞治疗中的应用

乳腺癌干细胞(CSCs)的分化疗法代表了一种重要的治疗癌症的策略,但对CSCs的低效递送阻碍了分化剂的功效。在这项工作中,我们报告了一种由合成的两亲树状聚合物构建的功能性树状体,该树状体可增强乳腺癌CSC的细胞摄取,通过携带全反式维甲酸(ATRA)来区分乳腺癌CSC,并通过携带ATRA和多西他赛来提高抗癌功效(DTX)在体外和在患有乳腺癌的小鼠中。该研究还通过分析乳腺癌CSCs分化治疗过程中的相关信号分子,转录因子和与细胞周期相关的信号通路,揭示了乳腺癌CSCs摄取细胞的机制,并揭示了分化机制。因此,

更新日期:2019-11-18
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