Docetaxel- and lemongrass oil-loaded niosomes modulate HMGA2-mediated cell cycle regulation in MCF-7 breast cancer cells

Abstract Niosomal delivery systems have emerged as promising nanocarriers for improving the delivery and therapeutic performance of anticancer agents. The chemotherapeutic agent docetaxel and the phytochemical lemongrass oil were separately encapsulated into niosomal formulations to evaluate whether niosomal delivery could enhance their biological performance and modulate HMGA2-associated cell-cycle regulation in the MCF-7 breast cancer model. The physicochemical properties of the produced niosomes were characterized. In vitro drug release, cytotoxicity against MCF-7 breast cancer cells and normal human skin fibroblast (HSF) cells, gene expression analysis of the HMGA2 signaling pathway, and molecular docking studies were also performed. Results indicated that citral (72.35%) was the main component of lemongrass oil. The niosomal formulations produced uniform, nanoscale vesicles with a negative zeta potential and high encapsulation efficiency. Effective encapsulation was confirmed through transmission electron microscopy and Fourier transform infrared spectroscopy, with no signs of chemical incompatibility. In vitro release studies showed a delayed release of both docetaxel and lemongrass oil from the niosomal systems compared to their free forms. Cytotoxicity studies revealed differential effects on MCF-7 and HSF cells, indicating selective anticancer activity of the tested formulations. Although niosomal encapsulation did not improve the in vitro selectivity index or cytotoxic potency compared with the corresponding free compounds, it provides potential therapeutic advantages through enhanced physicochemical stability, controlled drug release, and improved tumor-targeted delivery under in vivo conditions. Furthermore, the niosomal formulations significantly downregulated HMGA2 and key cell-cycle regulatory genes, suggesting induction of cell-cycle arrest and suppression of oncogenic signaling. Molecular docking supported these findings by demonstrating favorable interactions of docetaxel and citral with proteins involved in cell-cycle regulation. Collectively, these findings demonstrate the potential of niosomal encapsulation to enhance the therapeutic efficacy and selectivity of docetaxel and lemongrass oil in the MCF-7 breast cancer model and provide mechanistic insights into HMGA2-associated cell-cycle regulation, supporting further preclinical investigation of this nanocarrier platform. They also significantly downregulated HMGA2 and related cell-cycle regulatory genes, indicating activation of cell-cycle arrest and suppression of carcinogenic signaling. These findings demonstrate the potential of niosomal encapsulation to enhance the therapeutic efficacy of docetaxel and lemongrass oil in the MCF-7 breast cancer model and provide molecular insights into HMGA2-associated cell-cycle regulation, thereby supporting further preclinical investigation of this nanocarrier platform.