Targeted delivery of doxorubicin to HER2 positive tumor models

Hosna Gomari,1 Mehdi Forouzandeh Moghadam,1 Masoud Soleimani,2 Mahlegha Ghavami,1 Shabanali Khodashenas31Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 2Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Teh...

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Autores principales:	Gomari H, Forouzandeh Moghadam M, Soleimani M, Ghavami M, Khodashenas S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Exosome Breast cancer TUBO Targeted therapy Drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fd607917721945adb0d2a9ef99ae6bfa
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spelling	oai:doaj.org-article:fd607917721945adb0d2a9ef99ae6bfa2021-12-02T03:35:15ZTargeted delivery of doxorubicin to HER2 positive tumor models1178-2013https://doaj.org/article/fd607917721945adb0d2a9ef99ae6bfa2019-07-01T00:00:00Zhttps://www.dovepress.com/targeted-delivery-of-doxorubicin-to-her2-positive-tumor-models-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hosna Gomari,1 Mehdi Forouzandeh Moghadam,1 Masoud Soleimani,2 Mahlegha Ghavami,1 Shabanali Khodashenas31Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 2Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 3Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IranBackground: Exosomes are natural nanovesicles with unique characteristics, such as long circulating half-life, the intrinsic ability to target tissues, biocompatibility, and minimal or no inherent systemic toxicity. Mesenchymal stem cells produce large amounts of exosomes with regenerative properties and more stability in human plasma. TUBO breast cancer cell lines overexpress rat HER2/neu protein.Methods: Targeted exosomes were isolated from transduced bone marrow mesenchymal stem cells. Doxorubicin was encapsulated into exosomes by electroporation. Flow cytometry was used to assess the attachment of exosomes to the target cells. The in vitro cytotoxicity effect of targeted doxorubicin-loaded exosomes on TUBO cells was determined using MTT assay. Selective delivery of doxorubicin to tumor tissues was analyzed by measuring the auto-fluorescence of doxorubicin by in vivo imaging system. Moreover, tumor growth inhibition and body weight were monitored following injection of free doxorubicin, and targeted and untargeted doxorubicin-loaded exosomes in a TUBO breast cancer model. Finally, mouse tissues were examined for the presence of intrinsic ﬂuorescence of doxorubicin.Results: Flow cytometry results revealed significant differences in binding of targeted exosomes to HER2-positive (46.05%) and HER2-negative (13.9%) cells. The results of MTT assay showed that cytotoxicity of targeted doxorubicin-loaded exosomes was higher than free doxorubicin at 72 hours. Selective distribution of targeted doxorubicin-loaded exosomes in the target tissues of the murine breast cancer model suggested specific delivery of doxorubicin by targeted exosomes, rather than untargeted exosomes. Free doxorubicin and untargeted doxorubicin-loaded exosomes showed insignificant effects, whereas targeted doxorubicin-loaded exosomes reduced the tumor growth rate.Conclusion: Herein, we report efficient delivery of targeted doxorubicin-loaded exosomes in vitro, corroborated with a significant reduction of murine breast cancer model tumor growth rate.Keywords: exosome, breast cancer, TUBO, targeted therapy, drug deliveryGomari HForouzandeh Moghadam MSoleimani MGhavami MKhodashenas SDove Medical PressarticleExosomeBreast cancerTUBOTargeted therapyDrug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5679-5690 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Exosome Breast cancer TUBO Targeted therapy Drug delivery Medicine (General) R5-920
spellingShingle	Exosome Breast cancer TUBO Targeted therapy Drug delivery Medicine (General) R5-920 Gomari H Forouzandeh Moghadam M Soleimani M Ghavami M Khodashenas S Targeted delivery of doxorubicin to HER2 positive tumor models
description	Hosna Gomari,1 Mehdi Forouzandeh Moghadam,1 Masoud Soleimani,2 Mahlegha Ghavami,1 Shabanali Khodashenas31Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 2Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 3Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IranBackground: Exosomes are natural nanovesicles with unique characteristics, such as long circulating half-life, the intrinsic ability to target tissues, biocompatibility, and minimal or no inherent systemic toxicity. Mesenchymal stem cells produce large amounts of exosomes with regenerative properties and more stability in human plasma. TUBO breast cancer cell lines overexpress rat HER2/neu protein.Methods: Targeted exosomes were isolated from transduced bone marrow mesenchymal stem cells. Doxorubicin was encapsulated into exosomes by electroporation. Flow cytometry was used to assess the attachment of exosomes to the target cells. The in vitro cytotoxicity effect of targeted doxorubicin-loaded exosomes on TUBO cells was determined using MTT assay. Selective delivery of doxorubicin to tumor tissues was analyzed by measuring the auto-fluorescence of doxorubicin by in vivo imaging system. Moreover, tumor growth inhibition and body weight were monitored following injection of free doxorubicin, and targeted and untargeted doxorubicin-loaded exosomes in a TUBO breast cancer model. Finally, mouse tissues were examined for the presence of intrinsic ﬂuorescence of doxorubicin.Results: Flow cytometry results revealed significant differences in binding of targeted exosomes to HER2-positive (46.05%) and HER2-negative (13.9%) cells. The results of MTT assay showed that cytotoxicity of targeted doxorubicin-loaded exosomes was higher than free doxorubicin at 72 hours. Selective distribution of targeted doxorubicin-loaded exosomes in the target tissues of the murine breast cancer model suggested specific delivery of doxorubicin by targeted exosomes, rather than untargeted exosomes. Free doxorubicin and untargeted doxorubicin-loaded exosomes showed insignificant effects, whereas targeted doxorubicin-loaded exosomes reduced the tumor growth rate.Conclusion: Herein, we report efficient delivery of targeted doxorubicin-loaded exosomes in vitro, corroborated with a significant reduction of murine breast cancer model tumor growth rate.Keywords: exosome, breast cancer, TUBO, targeted therapy, drug delivery
format	article
author	Gomari H Forouzandeh Moghadam M Soleimani M Ghavami M Khodashenas S
author_facet	Gomari H Forouzandeh Moghadam M Soleimani M Ghavami M Khodashenas S
author_sort	Gomari H
title	Targeted delivery of doxorubicin to HER2 positive tumor models
title_short	Targeted delivery of doxorubicin to HER2 positive tumor models
title_full	Targeted delivery of doxorubicin to HER2 positive tumor models
title_fullStr	Targeted delivery of doxorubicin to HER2 positive tumor models
title_full_unstemmed	Targeted delivery of doxorubicin to HER2 positive tumor models
title_sort	targeted delivery of doxorubicin to her2 positive tumor models
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/fd607917721945adb0d2a9ef99ae6bfa
work_keys_str_mv	AT gomarih targeteddeliveryofdoxorubicintoher2positivetumormodels AT forouzandehmoghadamm targeteddeliveryofdoxorubicintoher2positivetumormodels AT soleimanim targeteddeliveryofdoxorubicintoher2positivetumormodels AT ghavamim targeteddeliveryofdoxorubicintoher2positivetumormodels AT khodashenass targeteddeliveryofdoxorubicintoher2positivetumormodels
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Targeted delivery of doxorubicin to HER2 positive tumor models

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