A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro

Hongxiang Wei,1,* Jinyuan Chen,2,* Shenglin Wang,1,* Feihuan Fu,3 Xia Zhu,1 Chaoyang Wu,1 Zhoujie Liu,4 Guangxian Zhong,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China; 2Department of Centrala...

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Main Authors: Wei H, Chen J, Wang S, Fu F, Zhu X, Wu C, Liu Z, Zhong G, Lin J
Format: Article
Language:English
Published: Dove Medical Press 2019-11-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/a-nanodrug-consisting-of-doxorubicin-and-exosome-derived-from-mesenchy-peer-reviewed-article-IJN
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author Wei H
Chen J
Wang S
Fu F
Zhu X
Wu C
Liu Z
Zhong G
Lin J
author_facet Wei H
Chen J
Wang S
Fu F
Zhu X
Wu C
Liu Z
Zhong G
Lin J
author_sort Wei H
collection DOAJ
description Hongxiang Wei,1,* Jinyuan Chen,2,* Shenglin Wang,1,* Feihuan Fu,3 Xia Zhu,1 Chaoyang Wu,1 Zhoujie Liu,4 Guangxian Zhong,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China; 2Department of Centralab, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China; 3Department of Endocrinology, The County Hospital of Anxi, Anxi 362400, People’s Republic of China; 4Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangxian Zhong; Jianhua LinDepartment of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of ChinaTel/fax +86 591 87981029Email zhongguangxian@163.com; jianhual@126.comPurpose: The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods: The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results: The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion: The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.Keywords: exosome, mesenchymal stem cells, doxorubicin, osteosarcoma  
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spelling doaj.art-ffaea1b0c4c44b5a96d9c0d9f44eb1292022-12-21T18:00:43ZengDove Medical PressInternational Journal of Nanomedicine1178-20132019-11-01Volume 148603861049466A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In VitroWei HChen JWang SFu FZhu XWu CLiu ZZhong GLin JHongxiang Wei,1,* Jinyuan Chen,2,* Shenglin Wang,1,* Feihuan Fu,3 Xia Zhu,1 Chaoyang Wu,1 Zhoujie Liu,4 Guangxian Zhong,1 Jianhua Lin1 1Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China; 2Department of Centralab, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China; 3Department of Endocrinology, The County Hospital of Anxi, Anxi 362400, People’s Republic of China; 4Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangxian Zhong; Jianhua LinDepartment of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of ChinaTel/fax +86 591 87981029Email zhongguangxian@163.com; jianhual@126.comPurpose: The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods: The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results: The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion: The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.Keywords: exosome, mesenchymal stem cells, doxorubicin, osteosarcoma  https://www.dovepress.com/a-nanodrug-consisting-of-doxorubicin-and-exosome-derived-from-mesenchy-peer-reviewed-article-IJNexosomemesenchymal stem cellsdoxorubicinosteosarcoma
spellingShingle Wei H
Chen J
Wang S
Fu F
Zhu X
Wu C
Liu Z
Zhong G
Lin J
A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
International Journal of Nanomedicine
exosome
mesenchymal stem cells
doxorubicin
osteosarcoma
title A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
title_full A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
title_fullStr A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
title_full_unstemmed A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
title_short A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro
title_sort nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro
topic exosome
mesenchymal stem cells
doxorubicin
osteosarcoma
url https://www.dovepress.com/a-nanodrug-consisting-of-doxorubicin-and-exosome-derived-from-mesenchy-peer-reviewed-article-IJN
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