The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin

Patrícia M.R. Pereira, Sandrina Silva, José S. Ramalho, Célia M. Gomes, Henrique Girão, José A.S. Cavaleiro, Carlos A.F. Ribeiro, João P.C. Tomé, Rosa Fernandes

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 PorGal8 effectiveness. We showed a specific uptake of PorGal8 and 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 PorGal8 in 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 PorGal8 enables selective target and cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1, preventing undesired phototoxicity in the surrounding healthy tissues.

Original languageEnglish
Pages (from-to)60-69
Number of pages10
JournalEuropean Journal of Cancer
Volume68
DOIs
StatePublished - Nov 1 2016

Keywords

  • Bladder cancer
  • Dendritic units of galactose
  • Galectin-1
  • Photodynamic therapy
  • Porphyrin

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