In this study, we propose a novel therapy system composed of UiO-66 nanoparticles, which contain quercetin combined with chloroquine (UQCNP), to achieve dual autophagy-ubiquitination blockade. Through UiO-66 NP drug loading, the solubility of quercetin (a proteasome inhibitor) was improved under physiological conditions, thereby increasing its effective concentration at the tumor site. The cell experiment results showed that UQCNP significantly increased the apoptosis rate of 4T1 cells by 73.6%, which was significantly higher than other groups. Transmission electron microscopy results showed that the autophagosome of cells in the UQCNP treatment group was significantly lower than that in other treatment groups. Moreover, western blot results showed that, compared with other groups, LC3 expression and proteasome activity (p < 0.01), as well as the tumor volume of mice treated with UQCNP (p < 0.01) were significantly reduced. These results indicate that UQCNP achieves effective tumor therapy by blocking the autophagy and proteasome pathways synchronously.

中文翻译：

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槲皮素@UiO-66 NPs和氯喹通过双重自噬-泛素化系统阻断联合治疗肿瘤

在本研究中，我们提出了一种由UiO-66纳米颗粒组成的新型治疗系统，其中含有槲皮素与氯喹（UQCNP）相结合，以实现自噬-泛素化双重阻断。通过UiO-66 NP载药，提高了槲皮素（一种蛋白酶体抑制剂）在生理条件下的溶解度，从而提高了其在肿瘤部位的有效浓度。细胞实验结果显示，UQCNP使4T1细胞的凋亡率显着增加73.6%，明显高于其他组。透射电镜结果显示，UQCNP处理组细胞自噬体显着低于其他处理组。此外，蛋白质印迹结果显示，与其他组相比，UQCNP治疗组小鼠的LC3表达和蛋白酶体活性（p <0.01）以及肿瘤体积（p <0.01）均显着减少。这些结果表明UQCNP通过同步阻断自噬和蛋白酶体途径实现了有效的肿瘤治疗。