Ultrasound-mediated mesoporous silica nanoparticles loaded with PDLIM5 siRNA inhibit gefitinib resistance in NSCLC cells by attenuating EMT.
Ultrasound-mediated mesoporous silica nanoparticles loaded with PDLIM5 siRNA inhibit gefitinib resistance in NSCLC cells by attenuating EMT.
复制标题
DOI：
10.1016/j.ejps.2023.106372
复制
发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
HaoAO Wu;Wenhao Lv;Yangyang Zhu;Ying-ying Jia;F. Nie
中科院分区：
文献类型：
--
作者：
HaoAO Wu;Wenhao Lv;Yangyang Zhu;Ying-ying Jia;F. Nie
表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKIs）是治疗非小细胞肺癌（NSCLC）的主要药物之一。既往研究表明PDZ和LIM结构域5（PDLIM 5）在EGFR TKI耐药中发挥重要作用。然而，没有通过抑制该基因来消除EGFR TKI耐药性的可行方法。在这里，我们配制了一种新的介孔二氧化硅负载PDLIM 5 siRNA（小干扰RNA）纳米平台。结果表明，PDLIM 5 siRNA能够有效地结合到纳米平台上，并具有良好的生物相容性。进一步的探索表明，纳米平台结合超声辐照可以非常有效地用于siRNA递送和超声成像。此外，PC-9吉非替尼耐药（PC-9/GR）细胞在耐药性发展过程中发生了上皮间质转化（EMT）变化。当PDLIM 5 siRNA进入PC-9/GR细胞后，耐药细胞对吉非替尼的敏感性可通过转化生长因子-β（TGF-β）/EMT途径恢复。因此，PDLIM 5可能是NSCLC细胞对吉非替尼耐药的重要原因，该纳米平台可能成为NSCLC患者EGFR TKI耐药的新治疗方法。
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKIs) was one of the main drugs in the treatment of non-small cell lung cancer (NSCLC). Previous studies had demonstrated that PDZ and LIM Domain 5 (PDLIM5) played an important role in EGFR TKIs resistance. However, there was no feasible method to eliminate EGFR TKIs resistance by suppressing this gene. Here, we formulated a novel mesoporous silica-loaded PDLIM5 siRNA (Small interfering RNA) nanoplatforms. The results have shown that PDLIM5 siRNA could be effectively bound to the nanoplatforms and had good biocompatibility. Further exploration suggested that the nano-platform combined with ultrasonic irradiation could be very effective for siRNA delivery and ultrasound imaging. Moreover, Epithelial-mesenchymal transformation (EMT) changes occurred in PC-9 Gefitinib resistance (PC-9/GR) cells during the development of drug resistance. When PDLIM5 siRNA entered PC-9/GR cells, the sensitivity of drug-resistant cells to gefitinib could be restored through the transforming growth factor-β (TGF-β)/EMT pathway. Therefore, PDLIM5 may be an important reason for the resistance of NSCLC cells to gefitinib, and this nanoplatform may become a novel treatment for EGFR TKIs resistance in NSCLC patients.