期刊
PLOS ONE
卷 9, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0095529
关键词
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资金
- FCT- Fundacao para a Ciencia e a Tecnologia, Portugal [PTDC/CTM/101538/2008]
- FCT
- Fundo Europeu de Desenvolvimento Regional (FEDER) [Pest-C/SAU/UI3282/2011, Pest-C/SAU/UI3282/2013, PEst-C/QUI/UI0062/2013]
- Fundação para a Ciência e a Tecnologia [PTDC/CTM/101538/2008] Funding Source: FCT
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 (PcGal(16)) 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 PcGal(16) induces cell death by generating oxidative stress. Although PDT with PcGal(16) 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. PcGal(16) co-localization with galectin-1 and GLUT1 and/or generation of oxidative stress after PcGal(16) 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 PcGal(16). The results reported herein show PcGal(16) 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.
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