Ruthenium-phthalocyanine compounds as photosensitizers for photodynamic therapy. Photochemical and photobiological aspects

• Grant number: 12/21232-4
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): February 01, 2013
• Effective date (End): January 31, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Santana da Silva
• Grantee: Laísa Bonafim Negri
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Nitric oxide (NO) is a biological messenger that has vital importance in many physiological processes, such as cardiovascular control, neural signaling and defense against microorganisms and tumors. In addition, NO is also tumorigenical which would enable the use of NO donors compounds in clinical treatments, for example in Photodynamic Therapy (PDT). Based on the chemical and biological characteristics of the NO is vital the search of systems capable of releasing NO in a controlled way for biological applications. One possibility involves nitrosyl ruthenium complexes whose strategy would be to use compounds that would be thermodynamically stable, but photochemically active.Compounds that absorb in the region of therapeutical window and are likely to propitiate photoinduced electron transfer may produce NO such ruthenium nitrosyl complexes. Based on that the goal of this project is the study of energy transfer and photoinduced electron in trans-[RuNO(pc-R) (NO2)] as producer of reactive oxygen species (ROS) and nitrogen (ERONs) by light irradiation in the region of 500 nm to 700 nm. Measurements of NO, singlet oxygen and its derivatives will be determined in different oxygen concentrations and the cytotoxicity in cancer cell lines, evaluated. Photochemical, photophysical and kinetic studies will be conducted in order to describe the electron transfer and photoinduced energy processes. Covalent binding of these species to an antibody specific for VEGF can promote double chemotherapeutic action, combining conventional chemotherapy and photodynamic therapy. The reason for this proposal, which relates to the selective disturbance of the endothelium of the tumor can improve the penetration of chemotherapeutic agents providing a synergistic effect between PDT and traditional chemotherapy. The use of this compound could also provide analysis by image, once phthalocyanines are fluorescents compounds. The work of Prof. Dr. Lea Ann Dailey as co-advisor, seeks to reconcile the experience gained by the researcher at King's College London in the area relating to solid tumors with experience of using coordination compounds in anticancer activity of this Brazilian group. Besides the student Laisa Bonafim Negri was an intern in those labs in 2011, as part of their undergraduate research. Recently FAPESP/Kings College London approved project of scientific cooperation between the teacher in charge - prof. Dr. Roberto Santana da Silva - and one researcher - Lea Ann Dailey - (2012/50588-1), enabling scientific exchange with the student applying for scholarship in this project. This certainly will allow a breakthrough in the area, a project already approved by FAPESP. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NEGRI, Laísa Bonafim. Ruthenium-phtalocyanines complexes such as photosensitizer in photodynamic therapy. Photochemical and photobiological aspects. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.