Galactodendritic phthalocyanine targets carbohydrate-binding proteins enhancing photodynamic therapy

• Published in: PloS one 2014-04, Vol.9 (4), p.e95529
• Main Authors: Pereira, Patrícia M R, Silva, Sandrina, Cavaleiro, José A S, Ribeiro, Carlos A F, Tomé, João P C, Fernandes, Rosa
• Format: Article
• Language: English
• Subjects: Analysis; Antioxidants; Apoptosis; Binding proteins; Binding sites; Biology and Life Sciences; Bladder; Bladder cancer; Cancer; Cancer therapies; Carbohydrates; Catalase - metabolism; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Chemical compounds; Chemical properties; Damage localization; Dendrimers - metabolism; Dendrimers - pharmacology; Efficiency; Galactose; Galectin 1 - genetics; Galectin 1 - metabolism; Galectin-1; Gene expression; Gene Knockdown Techniques; Glucose; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Glutathione Reductase - metabolism; Health aspects; Humans; Indoles - metabolism; Indoles - pharmacology; Inhibitory Concentration 50; Laboratories; Lectins; Life sciences; Light penetration; Localization; Medicine; Medicine and Health Sciences; Oxidative Stress; Oxygen; Pharmacology; Photoactivation; Photochemistry; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - metabolism; Photosensitizing Agents - pharmacology; Photosensitizing compounds; Phototoxicity; Phthalocyanins; Physical Sciences; Polysaccharides - metabolism; Polysaccharides - pharmacology; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Ribonucleic acid; RNA; siRNA; Superoxide Dismutase - metabolism; Thyroid gland; Tumor cell lines; Urinary bladder
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095529

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.