Vorinostat-eluting poly(DL-lactide-co-glycolide) nanofiber-coated stent for inhibition of cholangiocarcinoma cells
Authors Kwak TW, Lee HL, Song YH, Kim C, Kim JS, Seo SJ, Jeong YI, Kang DH
Received 16 May 2017
Accepted for publication 29 July 2017
Published 17 October 2017 Volume 2017:12 Pages 7669—7680
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Lakshmi Kiran Chelluri
Peer reviewer comments 3
Editor who approved publication: Dr Thomas Webster
Tae Won Kwak,1,* Hye Lim Lee,2,* Yeon Hui Song,2 Chan Kim,3 Jungsoo Kim,2 Sol-Ji Seo,2 Young-Il Jeong,2 Dae Hwan Kang2,4
1Medical Convergence Textile Center, Gyeongbuk, Republic of Korea; 2Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea; 3Amogreentech Co. Ltd. Gyeonggi-do, Republic of Korea; 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea
*These authors contributed equally to this work
Purpose: The aim of this study was to fabricate a vorinostat (Zolinza™)-eluting nanofiber membrane-coated gastrointestinal (GI) stent and to study its antitumor activity against cholangiocarcinoma (CCA) cells in vitro and in vivo.
Methods: Vorinostat and poly(DL-lactide-co-glycolide) dissolved in an organic solvent was sprayed onto a GI stent to make a nanofiber-coated stent using an electro-spinning machine. Intact vorinostat and vorinostat released from nanofibers was used to assess anticancer activity in vitro against various CCA cells. The antitumor activity of the vorinostat-eluting nanofiber membrane-coated stent was evaluated using HuCC-T1 bearing mice.
Results: A vorinostat-incorporated polymer nanofiber membrane was formed on the surface of the GI stent. Vorinostat was continuously released from the nanofiber membrane over 10 days, and its release rate was higher in cell culture media than in phosphate-buffered saline. Released vorinostat showed similar anticancer activity against various CCA cells in vitro compared to that of vorinostat. Like vorinostat, vorinostat released from nanofibers induced acetylation of histone H4 and inhibited histone deacetylases 1·3·4/5/7 expression in vitro and in vivo. Furthermore, vorinostat nanofibers showed a higher tumor growth inhibition rate in HuCC-T1 bearing mice than vorinostat injections.
Conclusion: Vorinostat-eluting nanofiber membranes showed significant antitumor activity against CCA cells in vitro and in vivo. We suggest the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment.
Keywords: vorinostat, nanofiber, GI stent, cholangiocarcinoma, drug eluting
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