Targeted breast cancer therapy using novel nanovesicle formulations of Olea europaea extract.

María Del Carmen Villegas-Aguilar, María de la Luz Cádiz-Gurrea, Andres Salumets, David Arráez-Román, Antonio Segura-Carretero, Alberto Sola-Leyva, María Paz Carrasco-Jiménez
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Abstract

Olive leaf is a byproduct of the olive tree that is rich in phenolic compounds with potential anticarcinogenic effects against various cancers, including breast cancer. Nevertheless, the ingestion or topical application of such plant extracts faces certain limitations. These limitations can be addressed by encapsulating the extracts in nanovesicles to enhance their release and bioavailability. This study aims to develop nanovesicles using Olea europaea leaf extract to exploit its potential anti-cancer properties. Soy lecithin was used to form liposomes for encapsulation of the olive leaf extract. In addition, ethanol and glycerol were added to form ethosomes and glycerosomes, respectively. The antiproliferative effect of both the free extract and the three formed nanovesicles was tested in MCF7 and MCF10A cell lines. To comprehend the mechanisms leading to reduced cell viability after exposure to olive leaf extract and its nanovesicles, levels of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptotic stage were evaluated. The results suggest that both, the nanovesicles and the free extract, are antiproliferative agents against MCF7 tumour cells. However, when examining the impact of olive leaf extract and the formulated nanovesicles on MCF10A cells, no reduction in cell viability was observed. Our findings indicate that the anti-tumour effect of the extract and its nanovesicles may be due to increased oxidative stress, mediated by mitochondrial damage. The mechanism through which olive leaf extract exerts its antiproliferative effect on the breast cancer tumour line implies that apoptosis may be induced by the extract via the involvement of a mitochondria-dependent ROS-mediated pathway.

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利用油橄榄提取物的新型纳米微粒制剂进行乳腺癌靶向治疗。
橄榄叶是橄榄树的副产品,富含酚类化合物,对包括乳腺癌在内的多种癌症具有潜在的抗癌作用。然而,此类植物提取物的摄入或局部应用面临一定的限制。这些限制可以通过将提取物封装在纳米微粒中来解决,以提高其释放和生物利用率。本研究旨在利用油橄榄叶提取物开发纳米微粒,以利用其潜在的抗癌特性。研究使用大豆卵磷脂形成脂质体,用于包裹橄榄叶提取物。此外,还加入乙醇和甘油,分别形成乙脂体和甘油体。在 MCF7 和 MCF10A 细胞系中测试了游离提取物和三种形成的纳米颗粒的抗增殖效果。为了了解细胞暴露于橄榄叶提取物及其纳米颗粒后存活率降低的机制,对活性氧(ROS)水平、线粒体膜电位和细胞凋亡阶段进行了评估。结果表明,纳米微粒和游离提取物都能抗 MCF7 肿瘤细胞的增殖。然而,在检测橄榄叶提取物和配制的纳米颗粒对 MCF10A 细胞的影响时,没有观察到细胞活力的降低。我们的研究结果表明,橄榄叶提取物及其纳米颗粒的抗肿瘤作用可能是由于线粒体损伤介导的氧化应激增加所致。橄榄叶提取物对乳腺癌肿瘤细胞株产生抗增殖作用的机制意味着,提取物可能通过线粒体依赖性 ROS 介导的途径诱导细胞凋亡。
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