Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma
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Hui-Ying Xue1,2,*, Yong Liu1,2,*, Jia-Zhi Liao1, Ju-Sheng Lin1, Bin Li2, Wei-Gang Yuan2, Robert J. Lee3, Lei Li2, Chuan-Rui Xu2, Xing-Xing He1
1Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA
*List of corporate first authors
Xing-Xing He, email: [email protected]
Chuan-Rui Xu, email: [email protected]
Lei Li, email: [email protected]
Keywords: microRNA, liver cancer, nanomedicine, therapy, AEG-1
Received: September 23, 2016 Accepted: November 02, 2016 Published: November 17, 2016
MiR-375 is a tumor suppressor miRNA that is downregulated in hepatocellular carcinoma (HCC). However, due to the lack of effective delivery strategies, miR-375 replacement as a therapy for HCC has not been investigated. In the present study, we have developed a straightforward strategy to deliver miR-375 into HCC cells by assembling miR-375 mimics on the surface of AuNPs and forming AuNP-miR-375 nanoparticles. AuNP-miR-375 exhibits high cellular uptake and preserves miR-375’s activities to suppress cellular proliferation, migration/invasion, and colony formation, and to induce apoptosis in HCC cells. Furthermore, AuNP-delivered miR-375 efficiently downregulated its target genes through RNA interference. In primary and xenograft tumor mouse models, AuNP-miR-375 showed high tumor uptake, therapeutic efficacy, and no apparent toxicity to the host mice. In conclusion, our findings indicate that AuNPs is a reliable strategy to deliver miR-375 into HCC cells and tissue, and that AuNP-miR-375 has the potential in the clinic for treatment of unresectable HCC.
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