title: Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.
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.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Gan
authors.initials: G
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Xili Hospital, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Chengming
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: The 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 ; School of Medicine, Shenzhen University, Shenzhen, People's Republic of China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The 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.
authors.forename: Laiqiang
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D014810:Vitamin E; D019833:Genistein; C014225:tocophersolan
keywords: TPGS-b-PCL; anticancer effect; cytotoxicity; drug delivery; genistein; nanomedicine
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