HSP32 (HO-1) inhibitor, copoly(styrene-maleic acid)-zinc protoporphyrin IX, a water-soluble micelle as anticancer agent: In vitro and in vivo anticancer effect

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Jun FangHiroshi Maeda

Abstract

We reported previously the antitumor effect of heme oxygenase-1 (HO-1) inhibition by zinc protoporphyrin IX (ZnPP). ZnPP per se is poorly water soluble and thus cannot be used as anticancer chemotherapeutic. Subsequently, we developed water-soluble micelles of ZnPP using styrene-maleic acid copolymer (SMA), which encapsulated ZnPP (SMA-ZnPP). In this report, the in vitro and in vivo therapeutic effects of SMA-ZnPP are described. In vitro experiments using 11 cultured tumor cell lines and six normal cell lines revealed a remarkable cytotoxicity of SMA-ZnPP against various tumor cells; average IC(50) is about 11.1 μM, whereas the IC(50) to various normal cells is significantly higher, that is, more than 50 μM. In the pharmacokinetic study, we found that SMA-ZnPP predominantly accumulated in the liver tissue after i.v. injection, suggesting its applicability for liver cancer. As expected, a remarkable antitumor effect was achieved in the VX-2 tumor model in the liver of rabbit that is known as one the most difficult tumor models to cure. Antitumor effect was also observed in murine tumor xenograft, that is, B16 melanoma and Meth A fibrosarcoma. Meanwhile, no apparent side effects were found even at the dose of ∼7 times higher conc...Continue Reading

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Citations

Mar 12, 2013·International Journal of Cell Biology·Simon C M Kwok
Aug 8, 2013·Future Medicinal Chemistry·Cedric P OwensCelia W Goulding
Nov 26, 2015·International Journal of Cancer. Journal International Du Cancer·Stefan FestHolger Christiansen
Dec 24, 2015·Oxidative Medicine and Cellular Longevity·A L FurfaroM Nitti
Jan 29, 2014·Contrast Media & Molecular Imaging·Nigel G Anderson, Anthony P Butler
Nov 10, 2013·Free Radical Biology & Medicine·Hye-Kyung Na, Young-Joon Surh
Dec 12, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hideaki NakamuraHiroshi Maeda
Dec 21, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Kenji TsukigawaHiroshi Maeda
May 6, 2017·Antioxidants·Mariapaola NittiAnna Lisa Furfaro
May 23, 2015·Nanomedicine·Patricia Coutinho de SouzaRheal A Towner
Feb 29, 2020·Molecular Neurobiology·Carlo Castruccio CastracaniGiovanni Li Volti
Apr 3, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshiharu Kaneo

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