Epithelial-to-mesenchymal transition (EMT) of carcinoma cells is a promising target for cancer therapy since it is closely related to tumor metastasis and therapeutic resistance. The process of EMT is strongly associated with epigenetic alterations in cancer cells. In addition, recent accumulating evidence suggests that EMT also has a significant influence on inducing cancer stem cells (CSCs). In this study, novel polymer core–lipid shell nanoparticles (PLNPs) are prepared to suppress cancer EMT by the combined effects of the antioxidant activity of core-encapsulated Mn imidazolium porphyrin (MnImP) and the epigenetic control by histone acetyltransferase-encoding plasmid DNA (pHAT) hybridized onto the shell surface. PLNPs show the ability to control the expression of EMT-related markers, resulting in the suppression of EMT in lung epithelial cancer cells (paraquat-treated A549 cells). Furthermore, PLNPs suppress the levels of intracellular mitochondrial ROS and the transformation to CSCs. The results of this study may provide a novel therapeutic strategy against tumor metastasis and treatment resistance.

中文翻译：

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用于抑制癌症转移的线粒体和表观遗传靶向纳米颗粒的制备

癌细胞的上皮间质转化（EMT）是癌症治疗的一个有前景的靶点，因为它与肿瘤转移和治疗抵抗密切相关。EMT 的过程与癌细胞的表观遗传改变密切相关。此外，最近越来越多的证据表明，EMT 对诱导癌症干细胞 (CSCs) 也有显着影响。在这项研究中，通过核心包裹的锰咪唑卟啉 (MnImP) 的抗氧化活性和组蛋白乙酰转移酶编码质粒 DNA 的表观遗传控制的联合作用，制备了新型聚合物核-脂质壳纳米粒子 (PLNPs) 来抑制癌症 EMT。 pHAT) 杂交到壳表面。PLNPs 显示出控制 EMT 相关标志物表达的能力，导致肺上皮癌细胞（百草枯处理的 A549 细胞）中 EMT 的抑制。此外，PLNPs 抑制细胞内线粒体 ROS 的水平和向 CSCs 的转化。这项研究的结果可能为对抗肿瘤转移和治疗耐药性提供一种新的治疗策略。