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A versatile polyion complex can intelligently respond to a tumor microenvironment to eliminate tumor stem cells for enhanced lung cancer targeted therapy.
Biomaterials Science ( IF 5.8 ) Pub Date : 2019-08-20 , DOI: 10.1039/c9bm00812h
Jiulong Zhang 1 , Xiufeng Zhao , Chunrong Yang , Ziyuan Huang , Menghao Shi , Shuang Pan , Haiyang Hu , Mingxi Qiao , Dawei Chen , Xiuli Zhao
Biomaterials Science ( IF 5.8 ) Pub Date : 2019-08-20 , DOI: 10.1039/c9bm00812h
Jiulong Zhang 1 , Xiufeng Zhao , Chunrong Yang , Ziyuan Huang , Menghao Shi , Shuang Pan , Haiyang Hu , Mingxi Qiao , Dawei Chen , Xiuli Zhao
Affiliation
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Poor prognosis in lung cancer has been proved to be associated with the presence of lung cancer stem cells (LCSCs). Similar to bulk cancer cells and always existing in the interior of a solid tumor, there are also insurmountable barriers for the elimination of CSCs. To overcome these drawbacks, a versatile polyion complex was rationally designed, which can respond to a tumor microenvironment and exhibits a size-variable property, which allows it to possess remarkable tumor penetration capability and to accumulate around LCSCs. Protein tyrosine kinase 7 (PTK7) antibody mediated active targetability can facilitate the cellular uptake of triphenylphosphine-docetaxel (TD) and microRNA-31(miR-31) and the breakage of the disulfide bond can also enhance intracellular drug release. TD possesses a favorable apoptosis-inducing effect via a mitochondria pathway, while miR-31 could significantly regulate the MET-PI3K-Akt signaling pathway to exert the capability to eliminate LCSCs. APSP/HA might support new insights into LCSC eradiation in cancer management.
中文翻译：
多功能的聚离子复合物可以智能地响应肿瘤微环境，消除肿瘤干细胞，从而增强肺癌靶向治疗。
事实证明，肺癌预后不良与肺癌干细胞（LCSC）的存在有关。与散装癌细胞相似，并且总是存在于实体瘤内部，消除CSCs也存在着不可逾越的障碍。为了克服这些缺点，合理地设计了一种通用的聚离子复合物，该复合物可以对肿瘤的微环境作出反应并具有大小可变的特性，从而使其具有显着的肿瘤穿透能力并在LCSC周围聚集。蛋白酪氨酸激酶7（PTK7）抗体介导的主动靶向性可以促进细胞摄取三苯膦-多西他赛（TD）和microRNA-31（miR-31），并且二硫键的断裂也可以增强细胞内药物的释放。TD通过线粒体途径具有良好的细胞凋亡诱导作用，而miR-31可以显着调节MET-PI3K-Akt信号传导途径，发挥消除LCSCs的能力。APSP / HA可能支持对LCSC放射治疗癌症的新见解。
更新日期：2019-07-29
中文翻译：
多功能的聚离子复合物可以智能地响应肿瘤微环境，消除肿瘤干细胞，从而增强肺癌靶向治疗。
事实证明，肺癌预后不良与肺癌干细胞（LCSC）的存在有关。与散装癌细胞相似，并且总是存在于实体瘤内部，消除CSCs也存在着不可逾越的障碍。为了克服这些缺点，合理地设计了一种通用的聚离子复合物，该复合物可以对肿瘤的微环境作出反应并具有大小可变的特性，从而使其具有显着的肿瘤穿透能力并在LCSC周围聚集。蛋白酪氨酸激酶7（PTK7）抗体介导的主动靶向性可以促进细胞摄取三苯膦-多西他赛（TD）和microRNA-31（miR-31），并且二硫键的断裂也可以增强细胞内药物的释放。TD通过线粒体途径具有良好的细胞凋亡诱导作用，而miR-31可以显着调节MET-PI3K-Akt信号传导途径，发挥消除LCSCs的能力。APSP / HA可能支持对LCSC放射治疗癌症的新见解。
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