Evaluation of the nitric oxide and singlet oxygen synergism produced by phthalocyanine ruthenium complexes in solid tumours. Photochemical, photophysical studies and in vitro and in vivo cytotoxicity measurements

• Grant number: 11/22594-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): February 01, 2013
• Effective date (End): November 05, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Santana da Silva
• Grantee: Loyanne Carla Barbosa Ramos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/23169-6 - Cytotoxicity and photo-cytotoxicity of new ruthenium-phthalocyanines compounds as nitric oxide and oxygen singlet producers in cancer cell lines: an innovative purpose for metal based drug, BE.EP.DR

Abstract

Nitric oxide (NO) is a biological messenger that has vital importance in many physiological processes, such as cardiovascular control, the neural signaling and defense against microorganisms and tumors. Furthermore, NO is also anticancer which would allow the use of NO donor compounds in clinical trials, for example, in Photodynamic Therapy (PDT). Based on chemical and biological characteristics of the NO molecule is that it is vital the search for systems capable of releasing NO in a controlled manner, in the biological system. One possibility involves the use of nitrosyl ruthenium complexes, whose strategy would be to use compounds that would be thermodynamically stable, but photochemically active. Compounds that absorb in the therapeutic window region and are capable of providing photoinduced electron transfer can, in the presence of ruthenium nitrosyl complexes, produce NO. Based on this the goal of this project is to study the energy transfer and photoinduced electron transfer in trans-[RuNO(pc-R)(NO2)] complex (pc-R is modified phthalocyanine with charge from -3 to -7) as producer agent of reactive oxygen (ROS) and nitrogen species (ERONs) by light irradiation in the region of 500 nm to 700 nm. Nitric oxide and singlet oxygen measurements will be determined for different oxygen concentrations and the cytotoxicity will be evaluated in cancer cell lines. Photochemical studies, by light irradiation in visible region will be held both in de-aerated medium as a function of oxygen concentration. NO quantification will be developed using NO-sensor and the photolysis will be also evaluated by UV-vis and FTIR spectrum analysis. Photophysical and kinetic methods will be conducted in order to describe the electron transfer and photoinduced energy processes. The citotoxical activity of trans-[RuNO(pc-R)(NO2)] complex that produce both nitric oxide (NO) and singlet oxygen (1O2) will be evaluated in vivo. Parallel studies will also be performed with trans-[RuNO(pc-R)(NO2)] encapsulated in liposomal delivery system.