Phototherapy using ruthenium-phthalocyanine complexes as generators of reactive oxygen and nitrogen species: study of the mechanism of action in vitro in different 2D and 3D models of cancer cells

• Grant number: 20/03367-6
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2021
• Effective date (End): July 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Roberto Santana da Silva
• Grantee: Amanda Blanque Becceneri
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cancer is a major public health problem worldwide and current treatments have limitations, such as the inability to completely eradicate tumor cells, high toxicity and lack of selectivity. To overcome these challenges, the combination of therapies has stood out as animportant strategy. Photodynamic Therapy (PDT) is a technique considered an ally to Cancer treatment because it is not invasive and has selectivity for tumor cells. This technique consists of using a photosensitizer (FS), which is activated by light with a specific wavelength, which can generate reactions that result in the release of free radicals such as singlet oxygen and can trigger death via apoptosis and/or necrosis. A limitation of this type of therapy is the need for the presence of oxygen, so to overcome this obstacle other molecules that produce oxygen-independent radical species have been used, such as Nitric Oxide (NO), which is known to participate in diferente physiological and pathological processes. This is also known for its anti-tumor action when in high concentrations and affinity for metals. Ruthenium complexes have already shown potential in the treatment of Cancer and are quite versatile for creating new complexes, in addition to being identified as NO donors. Previous assays performed by the group demonstrate the great potential of new NO-donor ruthenium complexes associated with PDT. Therefore, this project aims to evaluate the effects of NO donor ruthenium complexes and their variations in the presence and absence of irradiation associated with the PDT technique in tumor and non-tumor lines in 2D and 3D culture. Also, evaluations to analyze the effect of these complexes on bystander cells, which are not the direct target of the PDT, and coculture assays of tumor and non-tumor cells will be conducted in 2D and 3D cell culture model. (AU)