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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

Antitumor effect of genistein formulated in TPGS-b-PCL in comparison with pristine genistein and genistein-loaded PCL NPs (n=5).Notes: (A) Tumor growth curve of the BALB/c nude mice bearing HeLa cells xenograft after administration (*P<0.05); (B) body weight after administration; (C) weight of the tumor from each group taken out from the sacrificed mice at the end of the study (*P<0.05); (D) image of tumor from each group taken out from the sacrificed mice at the end of the study.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
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f11-ijn-10-2461: Antitumor effect of genistein formulated in TPGS-b-PCL in comparison with pristine genistein and genistein-loaded PCL NPs (n=5).Notes: (A) Tumor growth curve of the BALB/c nude mice bearing HeLa cells xenograft after administration (*P<0.05); (B) body weight after administration; (C) weight of the tumor from each group taken out from the sacrificed mice at the end of the study (*P<0.05); (D) image of tumor from each group taken out from the sacrificed mice at the end of the study.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.

Mentions: To compare the antitumor activity of genistein-loaded TPGS-b-PCL nanoformulation with that of the pristine genistein in vivo, HeLa cells were subcutaneously inoculated into the right flank of female BALB/c nude mice. When the tumor xenografts were touchable, mice were divided to three groups (n=5 for each group) and injected intraperitoneally every 2 days with saline, pristine genistein, genistein-loaded PCL NPs, or genistein-loaded TPGS-b-PCL NPs at the genistein dose of 50 mg/kg. As shown in Figure 11A, all the three genistein formulations significantly decreased the growth of HeLa tumor in vivo, with genistein-loaded TPGS-b-PCL NPs being more effective in comparison with pristine genistein and genistein-loaded PCL NPs. Moreover, all the three genistein formulations were well tolerated without significant impact on the mice body weight (Figure 11B). After treatment for 16 days, the mice were humanely killed and tumors were excised and weighted. As shown in Figure 11C, compared with saline group, the tumor weight in all the three genistein formulations-treated groups was significantly reduced, and the mice treated with genistein-loaded TPGS- b-PCL NPs exhibited the lightest tumor weight. Furthermore, the images of tumors from each group also indicated the advantages of genistein-loaded TPGS-b-PCL NPs versus pristine genistein and genistein-loaded PCL NPs in repressing tumor growth (Figure 11D). All animal care and procedures for animal experiments were with approval from the Administrative Committee on Animal Research in Tsinghua University.


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)

Antitumor effect of genistein formulated in TPGS-b-PCL in comparison with pristine genistein and genistein-loaded PCL NPs (n=5).Notes: (A) Tumor growth curve of the BALB/c nude mice bearing HeLa cells xenograft after administration (*P<0.05); (B) body weight after administration; (C) weight of the tumor from each group taken out from the sacrificed mice at the end of the study (*P<0.05); (D) image of tumor from each group taken out from the sacrificed mice at the end of the study.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
© Copyright Policy
Related In: Results  -  Collection

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

f11-ijn-10-2461: Antitumor effect of genistein formulated in TPGS-b-PCL in comparison with pristine genistein and genistein-loaded PCL NPs (n=5).Notes: (A) Tumor growth curve of the BALB/c nude mice bearing HeLa cells xenograft after administration (*P<0.05); (B) body weight after administration; (C) weight of the tumor from each group taken out from the sacrificed mice at the end of the study (*P<0.05); (D) image of tumor from each group taken out from the sacrificed mice at the end of the study.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
Mentions: To compare the antitumor activity of genistein-loaded TPGS-b-PCL nanoformulation with that of the pristine genistein in vivo, HeLa cells were subcutaneously inoculated into the right flank of female BALB/c nude mice. When the tumor xenografts were touchable, mice were divided to three groups (n=5 for each group) and injected intraperitoneally every 2 days with saline, pristine genistein, genistein-loaded PCL NPs, or genistein-loaded TPGS-b-PCL NPs at the genistein dose of 50 mg/kg. As shown in Figure 11A, all the three genistein formulations significantly decreased the growth of HeLa tumor in vivo, with genistein-loaded TPGS-b-PCL NPs being more effective in comparison with pristine genistein and genistein-loaded PCL NPs. Moreover, all the three genistein formulations were well tolerated without significant impact on the mice body weight (Figure 11B). After treatment for 16 days, the mice were humanely killed and tumors were excised and weighted. As shown in Figure 11C, compared with saline group, the tumor weight in all the three genistein formulations-treated groups was significantly reduced, and the mice treated with genistein-loaded TPGS- b-PCL NPs exhibited the lightest tumor weight. Furthermore, the images of tumors from each group also indicated the advantages of genistein-loaded TPGS-b-PCL NPs versus pristine genistein and genistein-loaded PCL NPs in repressing tumor growth (Figure 11D). All animal care and procedures for animal experiments were with approval from the Administrative Committee on Animal Research in Tsinghua University.

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