Proceedings Article | 14 August 2019
KEYWORDS: Photodynamic therapy, Oxidation, Picosecond phenomena, Photosensitizer targeting, Oxygen, Tissues, Modulation, Photochemistry, Cell death, Americium
Photosensitized oxidations are the key pharmacological reactions in Photodynamic Therapy (PDT). Several tissues and cellular targets have been shown to be responsible for the PDT response, but damage in membranes is key to modulate the mechanism as well as the overall efficiency of cell death.1 There are two major mechanisms of photosensitized oxidations, the direct-contact reactions with biological targets and the oxidations mediated by diffusing species, such as singlet oxygen. In a recent publication, we demonstrated that for a PS to fully compromise membrane function, it needs to be sacrificed through contact-dependent reactions, forming lipid-truncated aldehydes.2 In this presentation we will report data obtained with a series of Mg(II) porphyrazines (MgPzs), whose mechanism of photobleaching is not related with oxidation by singlet oxygen. By comparing the efficiency of membrane rupture by PSs with different electron-deficient fluorinated side groups, we showed that the higher the rate of photobleaching, which occurs because of a redox reaction with the lipid double bond, the faster the rate of membrane leakage. Therefore, our results indicate that the efficiency of causing membrane damage correlates with the efficiency of PS photobleaching, and consequently, PS regeneration should be exploited as an effective tool to developed improved PDT photosensitizers.
1. I Bacellar, et al. Photodynamic efficiency: from molecular photochemistry to cell death. Int. J. Mol. Sci. 2015, 16, 20523.
2. I Bacellar, et al. Photosensitized membrane permeabilization requires contact-dependent reactions between photosensitizer and lipids, J. Am. Chem. Soc. 2018, 140, 9606.
