Wang Shengpeng, Zhang Jinming, Wang Yitao, Chen Meiwan
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
Nanomedicine. 2016 Feb;12(2):411-20. doi: 10.1016/j.nano.2015.09.014. Epub 2015 Dec 19.
MicroRNAs (miRNAs) play critical roles in modulating the oncogenic driver pathways involved in the acquisition of resistance to cancer treatments. MiR-542-3p serves as a potent tumor suppressor molecule by targeting tumor suppressor p53 and apoptosis inhibitor survivin. A hyaluronic acid (HA)-decorated polyethylenimine-poly(d,l-lactide-co-glycolide) (PEI-PLGA) nanoparticle system was developed in this study for targeted co-delivery of doxorubicin (DOX) and miR-542-3p for triple negative breast cancer (TNBC) therapy. This system showed an average size at 131.7 nm and high drug encapsulation efficiency, and prevented miR-542-3p degradation in the serum. HA/PEI-PLGA nanoparticles increased both drug uptake and cytotoxicity in MDA-MB-231 cells compared to MCF-7 cells, which express lower CD44 levels. Intracellular restoration of miR-542-3p further promoted TNBC cell apoptosis via activating p53 and inhibiting survivin expression. These results indicate that HA/PEI-PLGA nanoparticles have the potential to co-deliver chemotherapeutic agents and tumor suppressive miRNAs in combinatorial TNBC therapy.
Breast cancer is a leading cause of mortality in women worldwide. The so-called triple negative tumors for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) usually signifies poor prognosis. In this article, the authors developed a hyaluronic acid (HA)-decorated polyethylenimine-poly(D,L-lactide-co-glycolide) (PEI-PLGA) nanoparticle system for the delivery of both doxorubicin (DOX) and miR-542-3p against this tumor sub-type. This may represent a promising new therapy to treat breast cancer patients in the near future.
微小RNA（miRNA）在调节参与癌症治疗耐药性获得的致癌驱动途径中发挥关键作用。MiR-542-3p通过靶向肿瘤抑制因子p53和凋亡抑制因子survivin发挥强大的肿瘤抑制分子作用。本研究开发了一种透明质酸（HA）修饰的聚乙烯亚胺-聚（d，l-丙交酯-共-乙交酯）（PEI-PLGA）纳米颗粒系统，用于三阴性乳腺癌（TNBC）治疗中阿霉素（DOX）和miR-542-3p的靶向共递送。该系统平均尺寸为131.7 nm，药物包封效率高，并能防止miR-542-3p在血清中降解。与表达较低CD44水平的MCF-7细胞相比，HA/PEI-PLGA纳米颗粒增加了MDA-MB-231细胞对药物的摄取和细胞毒性。miR-542-3p在细胞内的恢复通过激活p53和抑制survivin表达进一步促进TNBC细胞凋亡。这些结果表明，HA/PEI-PLGA纳米颗粒有潜力在联合TNBC治疗中共递送化疗药物和肿瘤抑制性miRNA。
乳腺癌是全球女性死亡的主要原因。雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）均为阴性的所谓三阴性肿瘤通常预示着预后不良。在本文中，作者开发了一种透明质酸（HA）修饰的聚乙烯亚胺-聚（D，L-丙交酯-共-乙交酯）（PEI-PLGA）纳米颗粒系统，用于针对这种肿瘤亚型递送阿霉素（DOX）和miR-542-3p。这可能代表了在不久的将来治疗乳腺癌患者的一种有前景的新疗法。
