Carboxymethyl Dextran-Stabilized Polyethylenimine-Poly(epsilon-caprolactone) Nanoparticles-Mediated Modulation of MicroRNA-34a Expression via Small-Molecule Modulator for Hepatocellular Carcinoma Therapy

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• 作者：Xiongwei Deng ; Zhaoxia Yin ; Zhixiang Zhou ; Yihui Wang ; Fang Zhang ; Qin Hu ; Yishu Yang ; Jianqing Lu ; Yan Wu ; Wang Sheng ; Yi Zeng
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：July 13, 2016
• 年：2016
• 卷：8
• 期：27
• 页码：17068-17079
• 全文大小：750K
• 年卷期：0
• ISSN：1944-8252

文摘

MicroRNA-34a (miR-34a) modulation therapy has shown great promise to treat hepatocellular carcinoma (HCC). 2′-Hydroxy-2,4,4′,5,6′-pentamethoxychalcone, termed Rubone, has been shown to specifically upregulate miR-34a expression in HCC cells and considered as novel anticancer agent. However, the extremely low aqueous solubility of Rubone hampers its use in cancer treatment. In the present study, surface-stabilized nanoparticles-based delivery strategy was engaged to overcome this impediment. In our preparation, Rubone was encapsulated in the micelles composed of polyethylenimine-poly(epsilon-caprolactone) (PEI-PCL) through hydrophobic interactions, which were subsequently stabilized with anionic carboxymethyl dextran CMD via electronic interaction. We found that Rubone-encapsulating nanoparticles are dispersed well in aqueous solution. The results further demonstrated that Rubone could be efficiently delivered in HCC cells by nanoparticles and upregulate miR-34a expression, which in turn led to inhibition of proliferation, migration, and increased apoptosis of HCC cells. In vivo experiments showed that Rubone can be preferentially delivered into tumor tissues by CMD-stabilized PEI-PCL nanoparticles after intravenous administration and significantly inhibited tumor growth. Furthermore, low cytotoxicity of the nanoparticles was observed in vitro and in vivo analyses, indicating a good compatibility of generated nanoparticles. The obtained results suggest that CMD-stabilized PEI-PCL nanoparticles may serve as a novel approach for small-molecule-modulator-mediated miR-34a restoration for HCC therapy.