MiR-375 Delivered by Lipid-coated Doxorubicin-Calcium Carbonate Nanoparticles Overcomes Chemoresistance in Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated...

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Bibliographic Details
Published in:Nanomedicine 2017-11, Vol.13 (8), p.2507-2516
Main Authors: Zhao, Pengxuan, Wu, Shuangping, Cheng, Yao, You, Jia, Chen, Yan, Li, Minsi, He, Chuanchuan, Zhang, Xiaojuan, Yang, Tan, Lu, Yao, Lee, Robert J, He, Xingxing, Xiang, Guangya
Format: Article
Language:English
Subjects:
Addictive effect
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - therapeutic use
Calcium Carbonate - chemistry
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - therapy
Cell Line, Tumor
Doxorubicin - administration & dosage
Doxorubicin - therapeutic use
Drug Delivery Systems
Drug resistance
Drug Resistance, Neoplasm
Hep G2 Cells
Humans
Internal Medicine
Lipids - chemistry
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Liver Neoplasms - therapy
Mice
Mice, Nude
MicroRNA
MicroRNAs - administration & dosage
MicroRNAs - therapeutic use
Nanomedicine
Nanoparticles - chemistry
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Summary:Abstract Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated calcium carbonate nanoparticles (LCC-DOX/miR-375 NPs), enhanced the anti-tumor effects through combination therapy, and were highly effective in reversing drug resistance in HCC. LCC-DOX/miR-375 NPs were prepared by a reverse microemulsions method. In vitro , LCC-DOX/miR-375 NPs exhibited enhanced intracellular accumulation, pH-sensitive DOX release and potent cytotoxicity. In vivo , LCC-DOX/miR-375 NPs showed efficient antitumor effect both in xenograft and primary HCC murine models. Our results showed that the LCC-DOX/miR-375 nanoparticles provide a novel strategy to overcome the drug resistance and promote addictive effect between miR-375 and DOX in HCC.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2017.05.010