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

Authors Wei H, Chen J, Wang S, Fu F, Zhu X, Wu C, Liu Z, Zhong G, Lin J

Received 10 June 2019

Accepted for publication 21 October 2019

Published 1 November 2019 Volume 2019:14 Pages 8603—8610

DOI https://doi.org/10.2147/IJN.S218988

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Mian Wang


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 work

Correspondence: Guangxian Zhong; Jianhua Lin
Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of China
Tel/fax +86 591 87981029
Email zhongguangxian@163.com; jianhual@126.com

Purpose: 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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