title: Water-soluble metalloporphyrinates with excellent photo-induced anticancer activity resulting from high tumor accumulation.
abstract: 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 IC50value (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.
authors.affiliation: Division of Pharmaceutical Sciences, Graduate School of Medical Science, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Tatsuto
authors.initials: T
authors.lastname: Kiwada
authors.affiliation: College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan. Electronic address: odani@p.kanazawa-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Odani
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins
keywords: Anticancer activity; High tumor accumulation; Photodynamic therapy (PDT); Pt(II)-based gallium(III) porphyrinates; Singlet oxygen