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Effect of the aggregation of phenothiazinium dyes on the photoinduced production of reactive oxygen species

Grant number: 18/11840-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2018
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Christiane Pavani
Grantee:Helenyce Reis do Nascimento
Home Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil

Abstract

Photodynamic Therapy is a therapeutic modality considered adjuvant or alternative for treatments of cancer, infectious processes and other diseases. The process is based on three components: visible light, a photosensitizer and oxygen. The photosensitizer selectively accumulates in the target tissue and upon activation by light, generates oxidative species which consequently cause cell death. There are two types of photochemical mechanisms in PDT: type I reactions that involve the production of different reactive oxygen species, mainly radicals and the type II reactions that result in the production of singlet oxygen. Due to the low cost, methylene blue, a phtnothiazinium dyes, has been an extremely widespread photosensitizer in Brazil. Other FS belonging to this class such as Azure A, Azure B and Dimethyl methylene blue, may be interesting for application in PDT since they present structural similarity to methylene blue (MB) and may present equivalent activity or even higher. Reports in the literature regarding the effectiveness of PDT with MB are conflicting. In particular, due to the physicochemical properties, MB may have its activity modulated by the medium in which it is transmitted because its mechanism of action is defined by its state of aggregation, but systematic studies with this approach are still scarce. In this sense, the identification of the relationships between aggregation, mechanism of action and effectiveness, as well as the establishment of means and formulations that may favor the most effective mechanism are essential. This work aims to quantify the production of reactive oxygen species generated by the photoactivation of phenothiazinium dyes Methylene Blue, Azure A, Azure B and Dimethyl methylene blue. Different mediumss will be used in which the aggregation of the photosensitizers can be modulated. It is desired to establish a relationship between the state of aggregation and the photochemical mechanism, type I (radical) or type II reaction (via singlet oxygen), in addition to comparing the oxidative potential of these photosensitizers.