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Improved therapeutic efficacy of quercetin-loaded polymeric nanoparticles on triple-negative breast cancer by inhibiting uPA

机译：通过抑制UPA改善槲皮素负载的聚合物纳米粒子对三阴性乳腺癌的治疗效果

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Triple negative breast cancer (TNBC) is one kind of breast cancer that demonstrates highly aggressive tumor biology. The high heterogeneity of TNBC makes its individual clinical treatment extremely blind and limited, which also introduces more challenges into the diagnosis and treatment of diseases. Urokinase-type plasminogen activator (uPA) is a high level marker for breast cancer, which mediates tumor growth and metastasis. Quercetin is a plant-derived flavonoid in many plants, which inhibits uPA and has low bioavailability and mediocre pharmaceutical efficacy. Thus, we herein developed polymeric nanoparticulate systems from PLGA-TPGS (Qu-NPs) for quercetin oral delivery and evaluated the anticancer effect of this formulation on TNBC in vitro and in vivo . Qu-NPs have a uniform spherical morphology with a mean diameter of 198.4 ± 7.8 nm and good drug loading capacity (8.1 ± 0.4%). Moreover, Qu-NPs exhibited significantly improved inhibition on the growth and metastasis in TNBC cells. Following oral gavage, a remarkable antitumor effect of Qu-NPs on 4T1-bearing mice was observed with a tumor inhibition ratio of 67.88% and fewer lung metastatic colonies. Furthermore, the inhibitory effect of quercetin on the migration of uPA knockdown MDA-MB231 cells was greatly attenuated. Together, Qu-NPs improved the significant antitumor and antimetastatic effects by inhibiting uPA, which provides a new strategy for the treatment of TNBC.
机译：三重阴性乳腺癌（TNBC）是一种乳腺癌，证明了高度侵略性的肿瘤生物学。 TNBC的高异质性使其个体临床治疗非常盲目和有限，这也引入了对疾病的诊断和治疗的更多挑战。尿激酶型纤溶酶原激活剂（UPA）是乳腺癌的高水平标志物，其介导肿瘤生长和转移。槲皮素是许多植物中的植物衍生的黄酮，其抑制UPA并具有低生物利用度和平庸的药物效果。因此，我们在本文中开发了来自PLGA-TPGS（QU-NPS）的聚合物纳米颗粒系统，用于槲皮素口服递送，并在体外和体内评估该配方对TNBC的抗癌效果。 QU-NPS具有均匀的球形形态，平均直径为198.4±7.8nm，良好的药物负载能力（8.1±0.4％）。此外，QU-NPS表现出显着提高对TNBC细胞生长和转移的抑制。口腔饲养后，观察到Qu-NPS在4T1轴承小鼠上的显着抗肿瘤效应，肿瘤抑制率为67.88％和肺转移菌落。此外，槲皮素对uPA敲低MDA-MB231细胞迁移的抑制作用大大衰减。在一起，qu-nps通过抑制UPA来改善显着的抗肿瘤和抗体效应，为治疗TNBC提供了一种新的策略。

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