Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

Huiying Xue,1 Zhaoyang Yu,1 Yong Liu,1 Weigang Yuan,1 Tan Yang,1 Jia You,1 Xingxing He,2 Robert J Lee,3 Lei Li,1 Chuanrui Xu1 1School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 2Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong U...

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Autores principales:	Xue H, Yu Z, Liu Y, Yuan W, Yang T, You J, He X, Lee RJ, Li L, Xu C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Hollow mesoporous silica nanoparticle doxorubicin miR-375 AEG-1 hepatocellular carcinoma multidrug resistance Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/59bfd9accc8a4792804806e1ebce1ade
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spelling	oai:doaj.org-article:59bfd9accc8a4792804806e1ebce1ade2021-12-02T02:01:31ZDelivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma1178-2013https://doaj.org/article/59bfd9accc8a4792804806e1ebce1ade2017-07-01T00:00:00Zhttps://www.dovepress.com/delivery-of-mir-375-and-doxorubicin-hydrochloride-by-lipid-coated-holl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Huiying Xue,1 Zhaoyang Yu,1 Yong Liu,1 Weigang Yuan,1 Tan Yang,1 Jia You,1 Xingxing He,2 Robert J Lee,3 Lei Li,1 Chuanrui Xu1 1School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 2Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 3Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA Abstract: Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/miR-375 overcame drug efflux and delivered miR-375 and DOX into MDR HepG2/ADR cells or HCC tissues. MiR-375 delivered by LHD/miR-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of miR-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/miR-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that miR-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of miR-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application. Keywords: hollow mesoporous silica nanoparticle, doxorubicin, miR-375, AEG-1, hepatocellular carcinoma, multidrug resistanceXue HYu ZLiu YYuan WYang TYou JHe XLee RJLi LXu CDove Medical PressarticleHollow mesoporous silica nanoparticledoxorubicinmiR-375AEG-1hepatocellular carcinomamultidrug resistanceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5271-5287 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hollow mesoporous silica nanoparticle doxorubicin miR-375 AEG-1 hepatocellular carcinoma multidrug resistance Medicine (General) R5-920
spellingShingle	Hollow mesoporous silica nanoparticle doxorubicin miR-375 AEG-1 hepatocellular carcinoma multidrug resistance Medicine (General) R5-920 Xue H Yu Z Liu Y Yuan W Yang T You J He X Lee RJ Li L Xu C Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
description	Huiying Xue,1 Zhaoyang Yu,1 Yong Liu,1 Weigang Yuan,1 Tan Yang,1 Jia You,1 Xingxing He,2 Robert J Lee,3 Lei Li,1 Chuanrui Xu1 1School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 2Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 3Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA Abstract: Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/miR-375 overcame drug efflux and delivered miR-375 and DOX into MDR HepG2/ADR cells or HCC tissues. MiR-375 delivered by LHD/miR-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of miR-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/miR-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that miR-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of miR-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application. Keywords: hollow mesoporous silica nanoparticle, doxorubicin, miR-375, AEG-1, hepatocellular carcinoma, multidrug resistance
format	article
author	Xue H Yu Z Liu Y Yuan W Yang T You J He X Lee RJ Li L Xu C
author_facet	Xue H Yu Z Liu Y Yuan W Yang T You J He X Lee RJ Li L Xu C
author_sort	Xue H
title	Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
title_short	Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
title_full	Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
title_fullStr	Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
title_full_unstemmed	Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
title_sort	delivery of mir-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/59bfd9accc8a4792804806e1ebce1ade
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Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

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