Improved therapeutic efficacy of quercetin-loaded polymeric nanoparticles on triple-negative breast cancer by inhibiting uPA.
Improved therapeutic efficacy of quercetin-loaded polymeric nanoparticles on triple-negative breast cancer by inhibiting uPA.
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通过抑制 uPA 提高槲皮素负载聚合物纳米颗粒对三阴性乳腺癌的治疗效果
作者：
三阴性乳腺癌（Triple Negative Breast Cancer，TNBC）是一种具有高度侵袭性的乳腺癌。TNBC的高度异质性使其个体化临床治疗具有极大的盲目性和局限性，这也给疾病的诊断和治疗带来了更多的挑战。尿激酶型纤溶酶原激活物（Urokinase-type plasminogen activator，uPA）是乳腺癌的高水平标志物，它介导肿瘤的生长和转移。槲皮素是一种存在于许多植物中的植物源性黄酮类化合物，其抑制uPA，生物利用度低，药效中等。因此，我们在本文中开发了用于槲皮素口服递送的来自PLGA-TPGS（Qu-NP）的聚合物纳米颗粒系统，并评估了该制剂在体外和体内对TNBC的抗癌作用。Qu-NP具有均匀的球形形态，平均直径为198.4 ± 7.8 nm，并且具有良好的载药量（8.1 ± 0.4%）。此外，Qu-NP对TNBC细胞的生长和转移表现出显著改善的抑制。经口灌胃给药后，Qu纳米粒对4 T1荷瘤小鼠有显著的抑瘤作用，抑瘤率为67.88%，肺转移集落较少。此外，槲皮素对uPA敲低的MDA-MB 231细胞的迁移抑制作用大大减弱。Qu纳米粒通过抑制uPA而提高了显著的抗肿瘤和抗转移作用，这为TNBC的治疗提供了新的策略。三阴性乳腺癌（Triple Negative Breast Cancer，TNBC）是一种具有高度侵袭性的乳腺癌。
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. Triple negative breast cancer (TNBC) is one kind of breast cancer that demonstrates highly aggressive tumor biology.
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影响因子：
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DOI：
10.1016/s1470-2045(14)70364-x
发表时间：
2014-12
期刊：
The Lancet. Oncology
影响因子：
--
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