Galactodendritic phthalocyanine targets carbohydrate-binding proteins enhancing photodynamic therapy.
Photosensitizers (PSs) are of crucial importance in the effectiveness of photodynamic therapy (PDT) for cancer. Due to their high reactive oxygen species production and strong absorption in the wavelength range between 650 and 850 nm, where tissue light penetration is rather high, phthalocyanines (Pcs) have been studied as PSs of excellence. In this work, we report the evaluation of a phthalocyanine surrounded by a carbohydrate shell of sixteen galactose units distributed in a dendritic manner (PcGal16) as a new and efficient third generation PSs for PDT against two bladder cancer cell lines, HT-1376 and UM-UC-3. Here, we define the role of galacto-dendritic units in promoting the uptake of a Pc through interaction with GLUT1 and galectin-1. The photoactivation of PcGal16 induces cell death by generating oxidative stress. Although PDT with PcGal16 induces an increase on the activity of antioxidant enzymes immediately after PDT, bladder cancer cells are unable to recover from the PDT-induced damage effects for at least 72 h after treatment. PcGal16 co-localization with galectin-1 and GLUT1 and/or generation of oxidative stress after PcGal16 photoactivation induces changes in the levels of these proteins. Knockdown of galectin-1 and GLUT1, via small interfering RNA (siRNA), in bladder cancer cells decreases intracellular uptake and phototoxicity of PcGal16. The results reported herein show PcGal16 as a promising therapeutic agent for the treatment of bladder cancer, which is the fifth most common type of cancer with the highest rate of recurrence of any cancer.
QOPNA and Department of Chemistry, University of Aveiro, Aveiro, Portugal; Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Coimbra, Portugal.
Patrícia M R
PM
Pereira
QOPNA and Department of Chemistry, University of Aveiro, Aveiro, Portugal.
Sandrina
S
Silva
QOPNA and Department of Chemistry, University of Aveiro, Aveiro, Portugal.
José A S
JA
Cavaleiro
Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Coimbra, Portugal.
Carlos A F
CA
Ribeiro
QOPNA and Department of Chemistry, University of Aveiro, Aveiro, Portugal; Department of Organic Chemistry, Ghent University, Gent, Belgium.
João P C
JP
Tomé
Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Coimbra, Portugal; Center of Investigation in Environment, Genetics and Oncobiology, Coimbra, Portugal; Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Rosa
R
Fernandes
D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000378:metabolism / Q000494:pharmacology*; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018384:Oxidative Stress; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D050091:Dendrimers; D037483:Galectin 1; D051272:Glucose Transporter Type 1; D007211:Indoles; C445499:LGALS1 protein, human; D017319:Photosensitizing Agents; D011134:Polysaccharides; D017382:Reactive Oxygen Species; C495677:SLC2A1 protein, human; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase