Hyaluronic acid-coated PEI-PLGA nanoparticles mediated co-delivery of doxorubicin and miR-542-3p for triple negative breast cancer therapy

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• 作者：Shengpeng Wang ; MS¹ ; Jinming Zhang ; MS¹ ; Yitao Wang ; MS ; ^{ytwang@umac.mo" class="auth_mail" title="E-mail the corresponding author} ; Meiwan Chen ; PhD ; ^{mwchen@umac.mo" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MicroRNA ; Doxorubicin ; Breast cancer ; Hyaluronic acid ; Apoptosis
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：12
• 期：2
• 页码：411-420
• 全文大小：1383 K

文摘

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.

From the Clinical Editor

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.