期刊
THERANOSTICS
卷 6, 期 1, 页码 142-154出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.13130
关键词
Hepatocellular Carcinoma; Co-delivery; miR-375; Cisplatin; Nanoparticles
资金
- Natural Science Foundation of China [81301235, 81370058]
- Natural Science Foundation of Hubei Province [2014CFB405]
- Independent Innovation Foundation of HUST [2014YGYL013]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120142120095]
- Fundamental Research Funds for the Central Universities of HUST [2014TS090]
One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 was fabricated by mixing two reverse microemulsions containing KCl solution and a highly soluble cis-diaminedihydroplatinum (II) coated with a cationic lipid layer. Subsequently, the miR-375 was incorporated into the lipid-coated cisplatin nanoparticles. The NPC/miR375 nanoparticles were expected to further decrease cell proliferation and to enhance the anti-tumor effect of cisplatin in chemotherapy resistant HCC cells. In vitro analysis of intracellular trafficking revealed that NPC/miR-375 were able to escape from the late endosomes instead of lysosomes thus avoiding degradation of the miR-375 in lysosomes. Importantly, NPC/miR-375 enhanced apoptosis and induced cell cycle arrest in HCC cells in vitro. In the double oncogenes Akt/Ras-induced primary HCC mouse model, multiple doses of NPC/miR-375 significantly inhibited tumor growth and delayed the tumor relapse. Our results indicate that cisplatin nanoparticles co-loaded with miR-375 represent a potential therapeutic agent for chemotherapy-insensitive HCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据