Water-soluble metalloporphyrinates with excellent photo-induced anticancer activity resulting from high tumor accumulation

作者：Hu Xiaojun; Ogawa Kazuma; Kiwada Tatsuto; Odani Akira

来源：Journal of Inorganic Biochemistry, 2017, 170: 1-7.

DOI：10.1016/j.jinorgbio.2017.02.001

• Pt(II)-based gallium(III) porphyrinates
• Photodynamic therapy (PDT)
• Singlet oxygen
• High tumor accumulation
• Anticancer activity

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 (Phi(Delta)) and remarkable photocytotoxicity with appreciable phototoxic indexes (PIs). In particular, Ga-4cisPtTPyP showed a low IC50 value (Colon 26: 0.12 mu M; Sarcoma 180: 0.08 mu M) 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.

• 出版日期2017-5