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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Water-soluble metalloporphyrinates with excellent photo-induced anticancer activity resulting from high tumor accumulation.
Journal of Inorganic Biochemistry 2017 May
To develop a water-soluble and tumor-targeted photosensitizer for photodynamic therapy (PDT), a porphyrin framework containing the metal ion gallium(III) was combined with platinum(II)-based groups to produce two new pentacationic metalloporphyrinates, Ga-4cisPtTPyP (5,10,15,20-tetrakis{cis-diammine-chloro-platinum(II)}(4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate) and Ga-4transPtTPyP (5,10,15,20-tetrakis{trans-diammine-chloro-platinum(II)} (4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate). Both complexes exhibited high singlet oxygen quantum yields (Φ∆ ) and remarkable photocytotoxicity with appreciable phototoxic indexes (PIs). In particular, Ga-4cisPtTPyP showed a low IC50 value (Colon 26: 0.12μM; Sarcoma 180: 0.08μM) under illumination and its PI up to 1000. With outstanding tumor accumulation (tumor/muscle ratio>9), Ga-4cisPtTPyP almost completely inhibited tumor growth over two weeks in an in vivo PDT assay. These results imply that Ga-4cisPtTPyP could be a promising anticancer agent for use in PDT.
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