Mitochondrial dysfunction may cause cancer and metabolic syndrome. Ellagic acid (abbreviated as E), a phytochemical, possesses anticancer activity. MicroRNA 125 (miR-125) may regulate metabolism. However, E has low aqueous solubility, and miR-125 is unstable in a biological fluid. Hence, this study aimed to develop nanoparticle formulations for the co-treatment of miR-125 and E. These nanoparticles were modified with one mitochondrion-directed peptide and a tumor-targeted ligand, and their modulating effects on mitochondrial dysfunction, antitumor efficacy, and safety in head and neck cancer (HNC) were evaluated. Results revealed that miR-125- and E-loaded nanoparticles effectively targeted cancer cells and intracellular mitochondria. The co-treatment significantly altered cellular bioenergetics, lipid, and glucose metabolism in human tongue squamous carcinoma SAS cells. This combination therapy also regulated protein expression associated with bioenergenesis and mitochondrial dynamics. These formulations also modulated multiple pathways of tumor metabolism, apoptosis, resistance, and metastasis in SAS cells. In vivo mouse experiments showed that the combined treatment of miR-125 and E nanoparticles exhibited significant hypoglycemic and hypolipidemic effects. The combinatorial therapy of E and miR-125 nanoparticles effectively reduced SAS tumor growth. To our best knowledge, this prospective study provided a basis for combining miRNA with a natural compound in nanoformulations to regulate mitochondrial dysfunction and energy metabolism associated with cancer.

中文翻译：

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线粒体定向的纳米粒子负载天然化合物和微小RNA，通过调节肿瘤代谢和线粒体动力学促进癌细胞死亡。

线粒体功能障碍可能导致癌症和代谢综合征。鞣花酸（缩写为E）是一种植物化学物质，具有抗癌活性。MicroRNA 125（miR-125）可能调节新陈代谢。但是，E的水溶性低，miR-125在生物液中不稳定。因此，本研究旨在开发可共同治疗miR-125和E的纳米颗粒制剂。这些纳米颗粒用一种线粒体定向肽和一种靶向肿瘤的配体进行修饰，以及它们对线粒体功能障碍，抗肿瘤功效和评估了头颈癌（HNC）的安全性。结果显示，载有miR-125和E的纳米颗粒可有效靶向癌细胞和细胞内线粒体。共同治疗显着改变了细胞生物能，脂质，舌鳞癌SAS细胞中的糖和葡萄糖代谢 这种联合疗法还调节与生物发生和线粒体动力学有关的蛋白质表达。这些制剂还调节了SAS细胞中肿瘤代谢，凋亡，抗性和转移的多种途径。体内小鼠实验表明，miR-125和E纳米颗粒的联合治疗表现出显着的降血糖和降血脂作用。E和miR-125纳米粒子的联合治疗有效降低了SAS肿瘤的生长。据我们所知，这项前瞻性研究为将miRNA与天然化合物结合在纳米制剂中以调节与癌症相关的线粒体功能障碍和能量代谢提供了基础。这种联合疗法还调节与生物发生和线粒体动力学有关的蛋白质表达。这些制剂还调节了SAS细胞中肿瘤代谢，凋亡，抗性和转移的多种途径。体内小鼠实验表明，miR-125和E纳米颗粒的联合治疗表现出显着的降血糖和降血脂作用。E和miR-125纳米粒子的联合治疗有效降低了SAS肿瘤的生长。据我们所知，这项前瞻性研究为将miRNA与天然化合物结合在纳米制剂中以调节与癌症相关的线粒体功能障碍和能量代谢提供了基础。这种联合疗法还调节与生物发生和线粒体动力学有关的蛋白质表达。这些制剂还调节了SAS细胞中肿瘤代谢，凋亡，抗性和转移的多种途径。体内小鼠实验表明，miR-125和E纳米颗粒的联合治疗表现出显着的降血糖和降血脂作用。E和miR-125纳米粒子的联合治疗有效降低了SAS肿瘤的生长。据我们所知，这项前瞻性研究为在纳米制剂中将miRNA与天然化合物结合以调节与癌症相关的线粒体功能障碍和能量代谢提供了基础。在SAS细胞中转移。体内小鼠实验表明，miR-125和E纳米颗粒的联合治疗表现出显着的降血糖和降血脂作用。E和miR-125纳米粒子的联合治疗有效降低了SAS肿瘤的生长。据我们所知，这项前瞻性研究为将miRNA与天然化合物结合在纳米制剂中以调节与癌症相关的线粒体功能障碍和能量代谢提供了基础。在SAS细胞中转移。体内小鼠实验表明，miR-125和E纳米颗粒的联合治疗表现出显着的降血糖和降血脂作用。E和miR-125纳米粒子的联合治疗有效降低了SAS肿瘤的生长。据我们所知，这项前瞻性研究为在纳米制剂中将miRNA与天然化合物结合以调节与癌症相关的线粒体功能障碍和能量代谢提供了基础。