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

Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L - Int J Nanomedicine (2015)

Bottom Line: The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

The molecular structure of genistein.
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f1-ijn-10-2461: The molecular structure of genistein.

Mentions: Many kinds of natural compounds derived from traditional Chinese medicine have been confirmed to have antitumor properties and also have little or no toxicity compared with synthetic chemicals.2 Flavonoids, including isoflavones, are natural polyphenolic compounds present ubiquitously in many plants and have antioxidant, anti-inflammatory, and antitumor properties.3,4 Genistein (4′,5,7-trihydroxyisoflavone, Figure 1) is one of the most abundant and best studied soy isoflavones and has received great attention for its many physiological functions, including potential antitumor activity.5,6 Recent studies have indicated that genistein could inhibit tumor cell growth and proliferation, arrest cell cycle at G2/M phase, suppress tumor migration, invasion, and angiogenesis, and induce apoptosis and autophagocytosis.7–11 However, the clinical use of genistein for cancer therapy was hindered by its poor water solubility and oral bioavailability. The emerging applications of nanotechnology-based cancer therapy provide a potent platform to improve poor water solubility and bioavailability of hydrophobic antitumor agents.12,13


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

Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L - Int J Nanomedicine (2015)

The molecular structure of genistein.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383221&req=5

f1-ijn-10-2461: The molecular structure of genistein.
Mentions: Many kinds of natural compounds derived from traditional Chinese medicine have been confirmed to have antitumor properties and also have little or no toxicity compared with synthetic chemicals.2 Flavonoids, including isoflavones, are natural polyphenolic compounds present ubiquitously in many plants and have antioxidant, anti-inflammatory, and antitumor properties.3,4 Genistein (4′,5,7-trihydroxyisoflavone, Figure 1) is one of the most abundant and best studied soy isoflavones and has received great attention for its many physiological functions, including potential antitumor activity.5,6 Recent studies have indicated that genistein could inhibit tumor cell growth and proliferation, arrest cell cycle at G2/M phase, suppress tumor migration, invasion, and angiogenesis, and induce apoptosis and autophagocytosis.7–11 However, the clinical use of genistein for cancer therapy was hindered by its poor water solubility and oral bioavailability. The emerging applications of nanotechnology-based cancer therapy provide a potent platform to improve poor water solubility and bioavailability of hydrophobic antitumor agents.12,13

Bottom Line: The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus