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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
- 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.
- Subjects :
- 0301 basic medicine
Sorafenib
Carcinoma, Hepatocellular
Liver tumor
Biomedical Engineering
Mice, Nude
Biochemistry
Calcium Carbonate
Biomaterials
Mice
03 medical and health sciences
0302 clinical medicine
Coated Materials, Biocompatible
In vivo
medicine
Animals
Humans
Cytotoxicity
neoplasms
Molecular Biology
Chemistry
Liver Neoplasms
Autophagy
Cancer
Hep G2 Cells
General Medicine
medicine.disease
Lipids
Xenograft Model Antitumor Assays
digestive system diseases
MicroRNAs
030104 developmental biology
Lipofectamine
Delayed-Action Preparations
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
Nanoparticles
Biotechnology
medicine.drug
Subjects
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