Combination of natural agents has received a great attention in cancer treatment because of synergistically increased apoptotic effect on cancer cell lines by triggering several apoptotic signaling pathways. However, the hydrophobic nature, poor bioavailability and low cellular uptake of most natural agents limit their therapeutic effectiveness. The purpose of this study was to design Apoferritin nanoparticles loaded with Quercetin and Curcumin (Que-Cur-HoS-Apo NPs) and to test their synergistic antitumor properties on a breast cancer cell line (MCF7). The physico-chemical characterization of the Que-Cur-HoS-Apo NPs by Size Exclusion Chromatography (FPLC) and Dynamic Light Scattering (DLS) confirmed the encapsulation of the compounds in the protein cage with narrow size distribution in the range 17.4 ± 1.2 nm. Cell viability study indicated that Que-Cur-HoS-Apo NPs were able to exert a more pronounced effect at lower dose on the MCF7 cell line when compared to the free combination of the drugs. The Que-Cur-HoS-Apo system allowed cellular uptake of natural agents thus triggering enhanced apoptosis. These effects were confirmed by Annexin-V/7-AAD Staining Assay and intracellular Reactive Oxygen Species (ROS) quantitative detection. These results suggest the potential of Que-Cur-HoS-Apo NPs as a promising anti-cancer agent in breast cancer therapy and pave the way to examine Que-Cur-HoS-Apo NPs effect in vivo.

中文翻译：

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槲皮素和姜黄素通过将它们加载到Apo铁蛋白腔中来有效协同作用对乳腺癌细胞凋亡的作用。

天然药物的组合在癌症治疗中受到了极大的关注，因为通过触发几种凋亡信号通路对癌细胞系的协同增效的凋亡作用。但是，大多数天然药物的疏水性，较差的生物利用度和较低的细胞摄取限制了它们的治疗效果。这项研究的目的是设计载有槲皮素和姜黄素（Que-Cur-HoS-Apo NPs）的载铁蛋白纳米颗粒，并测试它们在乳腺癌细胞系（MCF7）上的协同抗肿瘤特性。通过尺寸排阻色谱（FPLC）和动态光散射（DLS）对Que-Cur-HoS-Apo NP进行理化鉴定，证实了该化合物在蛋白笼中的包封具有窄的尺寸分布，范围为17.4±1.2 nm 。细胞活力研究表明，与药物的自由组合相比，Que-Cur-HoS-Apo NP在较低剂量下对MCF7细胞系具有更明显的作用。Que-Cur-HoS-Apo系统允许细胞吸收天然药物，从而触发增强的细胞凋亡。通过膜联蛋白-V / 7-AAD染色测定法和细胞内活性氧物种（ROS）定量检测证实了这些作用。这些结果表明Que-Cur-HoS-Apo NPs在乳腺癌治疗中有望成为一种有前景的抗癌药物，并为检验Que-Cur-HoS-Apo NPs在体内的作用铺平了道路。Que-Cur-HoS-Apo系统允许细胞吸收天然药物，从而触发增强的细胞凋亡。通过膜联蛋白-V / 7-AAD染色测定法和细胞内活性氧物种（ROS）定量检测证实了这些作用。这些结果表明Que-Cur-HoS-Apo NPs在乳腺癌治疗中有望成为一种有前景的抗癌药物，并为检验Que-Cur-HoS-Apo NPs在体内的作用铺平了道路。Que-Cur-HoS-Apo系统允许细胞吸收天然药物，从而触发增强的细胞凋亡。通过膜联蛋白-V / 7-AAD染色测定法和细胞内活性氧物种（ROS）定量检测证实了这些作用。这些结果表明Que-Cur-HoS-Apo NPs在乳腺癌治疗中有望成为一种有前景的抗癌药物，并为检验Que-Cur-HoS-Apo NPs在体内的作用铺平了道路。