Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Xiao Liang,* Yudi Wang,* Hui Shi, Mengmeng Dong, Haobo Han, Quanshun Li Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China*These authors contributed equally to this workC...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Liang X, Wang Y, Shi H, Dong M, Han H, Li Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	micelle aptamer nucleolin multidrug resistance tumor targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5768ac4b3d004a7d9d44385836814d03
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5768ac4b3d004a7d9d44385836814d03
record_format	dspace
spelling	oai:doaj.org-article:5768ac4b3d004a7d9d44385836814d032021-12-02T13:50:20ZNucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment1178-2013https://doaj.org/article/5768ac4b3d004a7d9d44385836814d032021-03-01T00:00:00Zhttps://www.dovepress.com/nucleolin-targeting-as1411-aptamer-modified-micelle-for-the-co-deliver-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiao Liang,* Yudi Wang,* Hui Shi, Mengmeng Dong, Haobo Han, Quanshun Li Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanshun Li; Haobo Han Tel/ Fax +86-431-85155200Email quanshun@jlu.edu.cn; hanhaobo@jlu.edu.cnBackground: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results: The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion: The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.Keywords: micelle, aptamer, nucleolin, multidrug resistance, tumor targetingLiang XWang YShi HDong MHan HLi QDove Medical Pressarticlemicelleaptamernucleolinmultidrug resistancetumor targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2569-2584 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	micelle aptamer nucleolin multidrug resistance tumor targeting Medicine (General) R5-920
spellingShingle	micelle aptamer nucleolin multidrug resistance tumor targeting Medicine (General) R5-920 Liang X Wang Y Shi H Dong M Han H Li Q Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
description	Xiao Liang,* Yudi Wang,* Hui Shi, Mengmeng Dong, Haobo Han, Quanshun Li Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanshun Li; Haobo Han Tel/ Fax +86-431-85155200Email quanshun@jlu.edu.cn; hanhaobo@jlu.edu.cnBackground: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results: The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion: The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.Keywords: micelle, aptamer, nucleolin, multidrug resistance, tumor targeting
format	article
author	Liang X Wang Y Shi H Dong M Han H Li Q
author_facet	Liang X Wang Y Shi H Dong M Han H Li Q
author_sort	Liang X
title	Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
title_short	Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
title_full	Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
title_fullStr	Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
title_full_unstemmed	Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment
title_sort	nucleolin-targeting as1411 aptamer-modified micelle for the co-delivery of doxorubicin and mir-519c to improve the therapeutic efficacy in hepatocellular carcinoma treatment
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/5768ac4b3d004a7d9d44385836814d03
work_keys_str_mv	AT liangx nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment AT wangy nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment AT shih nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment AT dongm nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment AT hanh nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment AT liq nucleolintargetingas1411aptamermodifiedmicelleforthecodeliveryofdoxorubicinandmir519ctoimprovethetherapeuticefficacyinhepatocellularcarcinomatreatment
_version_	1718392437406171136

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Ejemplares similares