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Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles

Authors :
Jia You
Guangya Xiang
Minsi Li
Yao Lu
Yan Chen
Yao Wang
Xiaojuan Zhang
Pengxuan Zhao
Chuanchuan He
Tan Yang
Robert J. Lee
Source :
Acta Biomaterialia. 72:248-255
Publication Year :
2018
Publisher :
Elsevier BV, 2018.

Abstract

Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy. In this study, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs). The nanoparticles had high loading efficiency and were ∼50 nm in diameter. Besides, the NPs could increase the stability and residence time of both drugs. Moreover, we demonstrated that autophagy was activated in HCC cells by sorafenib but not by miR-375/Sf-LCC NPs. In vitro, miR-375/Sf-LCC NPs exhibited pH-dependent drug release and potent cytotoxicity. In vivo, miR-375/Sf-LCC NPs increased miR-375 and sorafenib uptake in tumor (2 folds compared with Lipofectamine 2000-miR-375 and 2–5 folds compared with free sorafenib). Furthermore, miR-375/Sf-LCC NPs showed greatly enhanced therapeutic efficacy in an HCC xenograft model. These findings suggest that miR-375/Sf-LCC NPs may be a promising agent for the HCC therapy. Statement of Significance Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer mortality globally. In this manuscript, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs) to treat HCC. We demonstrated that miR-375/Sf-LCC NPs can deliver sorafenib and miR-375 into HCC cells and tumor tissues, increase drug retention time in tumor, significantly inhibit autophagy and produce enhanced anti-tumor effect.

Details

ISSN :
17427061
Volume :
72
Database :
OpenAIRE
Journal :
Acta Biomaterialia
Accession number :
edsair.doi.dedup.....ce394c7e59d5ccc9c8a434bbfd741136
Full Text :
https://doi.org/10.1016/j.actbio.2018.03.022