Preparation of Mitochondria- and Epigenetics-Targeting Nanoparticles for Suppression of Cancer Metastasis

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.