Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model

Xingang Liu,1 Jianmeng Wang,2 Weiguo Xu,3 Jianxun Ding,3 Bo Shi,4 Kexin Huang,4 Xiuli Zhuang,3 Xuesi Chen31Department of Critical Care Medicine, 2Department of Geriatrics, The First Hospital of Jilin University, 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applie...

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Autores principales: Liu XG, Wang JM, Xu WG, Ding JX, Shi B, Huang KX, Zhuang XL, Chen XS
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/2ba7a7962b6c44bd910dd39a29611c18
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spelling oai:doaj.org-article:2ba7a7962b6c44bd910dd39a29611c182021-12-02T00:36:36ZGlutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model1178-2013https://doaj.org/article/2ba7a7962b6c44bd910dd39a29611c182015-10-01T00:00:00Zhttps://www.dovepress.com/glutathione-degradable-drug-loaded-nanogel-effectively-and-securely-su-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xingang Liu,1 Jianmeng Wang,2 Weiguo Xu,3 Jianxun Ding,3 Bo Shi,4 Kexin Huang,4 Xiuli Zhuang,3 Xuesi Chen31Department of Critical Care Medicine, 2Department of Geriatrics, The First Hospital of Jilin University, 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 4Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun, People’s Republic of ChinaAbstract: The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significant higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.Keywords: antitumor efficacy, chemotherapy, controlled release, nanogel, reduction-responsiveness, securityLiu XGWang JMXu WGDing JXShi BHuang KXZhuang XLChen XSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6587-6602 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Liu XG
Wang JM
Xu WG
Ding JX
Shi B
Huang KX
Zhuang XL
Chen XS
Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
description Xingang Liu,1 Jianmeng Wang,2 Weiguo Xu,3 Jianxun Ding,3 Bo Shi,4 Kexin Huang,4 Xiuli Zhuang,3 Xuesi Chen31Department of Critical Care Medicine, 2Department of Geriatrics, The First Hospital of Jilin University, 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 4Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun, People’s Republic of ChinaAbstract: The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significant higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.Keywords: antitumor efficacy, chemotherapy, controlled release, nanogel, reduction-responsiveness, security
format article
author Liu XG
Wang JM
Xu WG
Ding JX
Shi B
Huang KX
Zhuang XL
Chen XS
author_facet Liu XG
Wang JM
Xu WG
Ding JX
Shi B
Huang KX
Zhuang XL
Chen XS
author_sort Liu XG
title Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
title_short Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
title_full Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
title_fullStr Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
title_full_unstemmed Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
title_sort glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/2ba7a7962b6c44bd910dd39a29611c18
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