Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Ying Fang,1,* Hao Wang,2,* Hong-Jing Dou,2,* Xing Fan,1,* Xiao-Chun Fei,3 Lei Wang,2 Shu Cheng,1 Anne Janin,4,5 Li Wang,1,4 Wei-Li Zhao1,4 1State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shangh...

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Autores principales:	Fang Y, Wang H, Dou HJ, Fan X, Fei XC, Wang L, Cheng S, Janin A, Zhao WL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	anti-lymphoma activity targeted therapy doxorubicin-loaded dextran nano-carrier cardiac toxicity. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a7e2d42d6f694d53baba24592664ba35
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spelling	oai:doaj.org-article:a7e2d42d6f694d53baba24592664ba352021-12-02T02:52:42ZDoxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity1178-2013https://doaj.org/article/a7e2d42d6f694d53baba24592664ba352018-09-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-loaded-dextran-based-nano-carriers-for-highly-efficient-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ying Fang,1,* Hao Wang,2,* Hong-Jing Dou,2,* Xing Fan,1,* Xiao-Chun Fei,3 Lei Wang,2 Shu Cheng,1 Anne Janin,4,5 Li Wang,1,4 Wei-Li Zhao1,4 1State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China; 3Department of Pathology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4Sino-French Research Center of Life Science and Genomics, Laboratory of Molecular Pathology, Shanghai, China; 5Joint Research Unit 1165, Inserm, University Paris VII, Saint-Louis Hospital, Paris, France *These authors contributed equally to this work Purpose: Cardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity. Methods: Inspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH)as much as that in systemic circulation condition (pH 7.4). Results: Lymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2. Conclusion: Dox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma. Keywords: anti-lymphoma activity, targeted therapy, doxorubicin-loaded, dextran, nano-carrier, cardiac toxicityFang YWang HDou HJFan XFei XCWang LCheng SJanin AWang LZhao WLDove Medical Pressarticleanti-lymphoma activitytargeted therapydoxorubicin-loadeddextrannano-carriercardiac toxicity.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5673-5683 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-lymphoma activity targeted therapy doxorubicin-loaded dextran nano-carrier cardiac toxicity. Medicine (General) R5-920
spellingShingle	anti-lymphoma activity targeted therapy doxorubicin-loaded dextran nano-carrier cardiac toxicity. Medicine (General) R5-920 Fang Y Wang H Dou HJ Fan X Fei XC Wang L Cheng S Janin A Wang L Zhao WL Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
description	Ying Fang,1,* Hao Wang,2,* Hong-Jing Dou,2,* Xing Fan,1,* Xiao-Chun Fei,3 Lei Wang,2 Shu Cheng,1 Anne Janin,4,5 Li Wang,1,4 Wei-Li Zhao1,4 1State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China; 3Department of Pathology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4Sino-French Research Center of Life Science and Genomics, Laboratory of Molecular Pathology, Shanghai, China; 5Joint Research Unit 1165, Inserm, University Paris VII, Saint-Louis Hospital, Paris, France *These authors contributed equally to this work Purpose: Cardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity. Methods: Inspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH)as much as that in systemic circulation condition (pH 7.4). Results: Lymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2. Conclusion: Dox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma. Keywords: anti-lymphoma activity, targeted therapy, doxorubicin-loaded, dextran, nano-carrier, cardiac toxicity
format	article
author	Fang Y Wang H Dou HJ Fan X Fei XC Wang L Cheng S Janin A Wang L Zhao WL
author_facet	Fang Y Wang H Dou HJ Fan X Fei XC Wang L Cheng S Janin A Wang L Zhao WL
author_sort	Fang Y
title	Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
title_short	Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
title_full	Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
title_fullStr	Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
title_full_unstemmed	Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
title_sort	doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/a7e2d42d6f694d53baba24592664ba35
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Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

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