title: The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin.
abstract: Conventional photodynamic agents used in clinic are porphyrin-based photosensitizers. However, they have low tumour selectivity, which may induce unwanted side-effects and damage to healthy tissues. In this study, we used a porphyrin with dendritic units of galactose (PorGal8) developed by us, which can target the galactose-binding protein, galectin-1, known to be overexpressed in many tumour tissues. In vitro and in vivo studies had been conducted for the validation of PorGal8effectiveness. We showed a specific uptake of PorGal8and induction of apoptotic cell death by generating oxidative stress and alterations in the cytoskeleton of bladder cancer cells overexpressing galectin-1. We further validated the photodynamic efficiency of PorGal8in athymic nude mice (Balb/c nu/nu) bearing subcutaneously implanted luciferase-positive bladder cancer xenografts, overexpressing galectin-1 protein. PorGal8(5 μmol/kg, intraperitoneal), injected 24 h before light delivery (50.4 J/cm2), inhibited tumour growth. We conclude that the use of PorGal8enables selective target and cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1, preventing undesired phototoxicity in the surrounding healthy tissues.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: Pereira
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Silva
authors.affiliation: Faculty of Medical Sciences, CEDOC, New University of Lisbon, Portugal.
authors.forename: José S
authors.initials: JS
authors.lastname: Ramalho
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Célia M
authors.initials: CM
authors.lastname: Gomes
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Girão
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: José A S
authors.initials: JA
authors.lastname: Cavaleiro
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Carlos A F
authors.initials: CA
authors.lastname: Ribeiro
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; Department of Organic and Macromolecular Chemistry, Ghent University, B-9000 Gent, Belgium; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: jtome@ua.pt.
authors.forename: João P C
authors.initials: JP
authors.lastname: Tomé
authors.affiliation: IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI, University of Coimbra, 3004-504 Coimbra, Portugal; Center of Investigation in Environment, Genetics and Oncobiology, 3001-301 Coimbra, Portugal. Electronic address: rcfernandes@fmed.uc.pt.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D050091:Dendrimers / Q000494:pharmacology*; D005690:Galactose / Q000494:pharmacology*; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D050091:Dendrimers; D037483:Galectin 1; D011166:Porphyrins; D005690:Galactose
keywords: Bladder cancer; Dendritic units of galactose; Galectin-1; Photodynamic therapy; Porphyrin