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Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

Authors Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L

Received 9 December 2014

Accepted for publication 16 February 2015

Published 27 March 2015 Volume 2015:10(1) Pages 2461—2473

DOI https://doi.org/10.2147/IJN.S78988

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Hongling Zhang,1,2* Gan Liu,1,2* Xiaowei Zeng,1,2 Yanping Wu,1,2 Chengming Yang,3 Lin Mei,1,2 Zhongyuan Wang,2,4 Laiqiang Huang1,2

1School of Life Sciences, Tsinghua University, Beijing, People’s Republic of China; 2The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People’s Republic of China; 3Xili Hospital, Shenzhen, Guangdong, People’s Republic of China; 4School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China

*These authors contributed equally to this work

Abstract: Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

Keywords: nanomedicine, genistein, TPGS-b-PCL, drug delivery, anticancer effect, cytotoxicity

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