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Study of the central metal effect on the photosensitizing properties of cationic porphyrins in liposomes and in cell cultures in vitro

Grant number: 18/05853-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2018
Effective date (End): November 30, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Mauricio da Silva Baptista
Grantee:Rodrigo Pinheiro Braga
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Photodynamic therapy has been consolidating itself as an alternative or additional treatment to the cancer conventional treatments, as surgery, chemo and radiotherapy. The discovery of new photosensitizers with improved properties for higher efficiency and fast treatment with minimum side effects represents a major challenge in the area. Porphyrins have been extensively investigated for such purpose since they show high molar absorptivity and efficient production of oxygen reactive species (ROS), which are responsible for the oxidation of biomolecules and cell death induction. Recently, it was demonstrated by our group that the coupling of [PtCl(bipy)]+ complexes at the periphery of the free-base tetrapyridylporphyrin (TPyP) ring significantly enhances the phototoxicity of the compound. Following these results we were motivated to investigate the effect of the coordination of metallic ions on the photodynamic potential of this platinated TPyP (PtPyP), considering that completely different responses were reported in the literature for different porphyrin macrocycles. For so, we propose to deeply investigate the photophysics of PtTPyPs coordinated to Zn(II), Ni(II) or Cu(II), studying their interaction with lipid membranes in liposomes and with tumor cells in vitro. It is expected that the central ion may not only modulate the efficiency of ROS production but modulate the porphyrin mechanism of action through the interaction with biomolecules present in the medium. (AU)