A versatile polyion complex can intelligently respond to a tumor microenvironment to eliminate tumor stem cells for enhanced lung cancer targeted therapy
A versatile polyion complex can intelligently respond to a tumor microenvironment to eliminate tumor stem cells for enhanced lung cancer targeted therapy
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多功能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
DOI：
10.1039/c9bm00812h
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发表时间：
2019
影响因子：
6.6
通讯作者：
Xiuli Zhao
中科院分区：
文献类型：
--
作者：
Jiulong Zhang;Xiufeng Zhao;Chunrong Yang;Ziyuan Huang;Menghao Shi;Shuang Pan;Haiyang Hu;Mingxi Qiao;Dawei Chen;Xiuli Zhao
肺癌预后不良与肺癌干细胞（LCSCs）的存在有关。与块状癌细胞类似，总是存在于实体瘤的内部，CSCs的消除也存在不可逾越的障碍。为了克服这些缺点，合理设计了一种通用的聚离子复合物，它可以响应肿瘤微环境，并表现出尺寸可变的特性，这使得它具有显着的肿瘤穿透能力，并在LCSC周围积累。蛋白酪氨酸激酶7（PTK 7）抗体介导的主动靶向性可促进三苯基膦-多西他赛（TD）和microRNA-31（miR-31）的细胞摄取，二硫键的断裂也可增强细胞内药物释放。TD通过线粒体途径具有良好的促凋亡作用，而miR-31可显著调节MET-PI 3 K-Akt信号通路发挥清除LCSC的能力。APSP/HA可能支持对LCSC放射治疗癌症的新见解。
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.