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

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.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Zhao P,Li M,Wang Y,Chen Y,He C,Zhang X,Yang T,Lu Y,You J,Lee RJ,Xiang G

doi

10.1016/j.actbio.2018.03.022

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

248-255

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(18)30142-9

journal_volume

72

pub_type

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