TY - JOUR
T1 - The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin
AU - Pereira, Patrícia M.R.
AU - Silva, Sandrina
AU - Ramalho, José S.
AU - Gomes, Célia M.
AU - Girão, Henrique
AU - Cavaleiro, José A.S.
AU - Ribeiro, Carlos A.F.
AU - Tomé, João P.C.
AU - Fernandes, Rosa
N1 - Funding Information:
This work was primarily supported with funds from the Foundation for Science and Technology (Portugal) ( PEst-C/SAU/UI3282/2011-2013 , UID/NEU/04539/2013 , FCT UID/QUI/00062/2013 and FCT UID/QUI/0100/2013 ) and COMPETE/FEDER . This work was also supported by ACIMAGO (ref. 12/12). The authors also acknowledge Fundação para a Ciência e Tecnologia (FCT-Portugal) for the postdoctoral and doctoral research grants SFRH/BPD/64812/2009 (to SS) and SFRH/BD/85941/2012 (to PMRP), respectively.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Bladder cancer
KW - Dendritic units of galactose
KW - Galectin-1
KW - Photodynamic therapy
KW - Porphyrin
UR - http://www.scopus.com/inward/record.url?scp=84990857207&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2016.08.018
DO - 10.1016/j.ejca.2016.08.018
M3 - Article
C2 - 27718388
AN - SCOPUS:84990857207
SN - 0959-8049
VL - 68
SP - 60
EP - 69
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -