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Chemo-phototherapeutic process of phthalocyanine-ruthenium system and cisplatin: chemical and photobiological evaluation in aqueous solution and in drug delivery system

Grant number: 15/03746-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2015
Effective date (End): August 31, 2019
Field of knowledge:Health Sciences - Pharmacy
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
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
Associated scholarship(s):17/00599-0 - Synergistic effect of low level light therapy, photodynamic therapy and chemotherapy using ruthenium phthalocianines and cisplatin as novel approach for cancer treatment, BE.EP.DR


Nitric oxide (NO) is a signaling biological molecule that is involved a vital role in many physiological processes, acting in cardiovascular control, neural signaling, tumor activity and defense mechanisms against microorganisms. In addition, NO is also known as anticancer agent which would enable the use of NO donor's compounds in clinical treatments, for example in Photodynamic Therapy (PDT). The intense search for systems which may release NO in a controlled manner in biological medium is related to the interesting chemical and biological properties of this molecule. One of the imminent possibilities involves the strategy of using nitrosyl ruthenium complexes, that are thermodynamically stable compounds, but photochemically active. In general, compounds with absorption in the therapeutic window and a ligand nitrosyl in its structure are likely to ensure photoinduced electron transfer to release NO. Based on these facts, the aim of this project is to evaluate synergistic effect of compounds susceptible to chemotherapeutic and phototherapeutic action from a drug delivery system containing ruthenium- phthalocyanine complex and cisplatin. A detailed study that involves a photoinduced energy and electron transfer processes in [Ru (Pc-DMX) 4 (NO) (ONO)] complex as producing agent of reactive oxygen (ROS) and nitrogen (ERONs) species by light irradiation in the 500 nm to 700 nm region. Measurements of NO, singlet oxygen and its derivatives shall be determined on the basis of different concentrations of oxygen and the cytotoxic potential in cancer cell lines will be evaluated as well. Photochemical, photophysical and kinetic studies will be conducted in order to describe the processes of photoinduced electron and energy transfer, observed in the species under study. Some biochemical processes related to the interaction between ruthenium complex and cells will be evaluated: the interaction of ruthenium complex with cell surface proteoglycans by labeling with fluorophores; Akt and mitogen-activated protein kinase (MAPK) phosphorylation; evaluation of AMPK (kinase protein AMP-activated), JNK (c-jun terminal kinase-N) and ATF3 (activation transcription factor 3).The cytotoxic potential of species that produce both nitric oxide (NO) and singlet oxygen (1O2) for photodynamic therapy of cancer will be evaluated. At the same time will be performed photochemical and photophysical studies quantifying the production of ROS and ERONs in the presence of a nanoparticule based delivery system. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NEGRI, LAISA BONAFIM; MARTINS, TASSIA JOI; DA SILVA, ROBERTO SANTANA; HAMBLIN, MICHAEL R.. Photobiomodulation combined with photodynamic therapy using ruthenium phthalocyanine complexes in A375 melanoma cells: Effects of nitric oxide generation and ATP production. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 198, . (16/12707-0, 15/03746-9)
NEGRI, LAISA B.; MARTINS, TASSIA J.; DA SILVA GOBO, NICHOLAS R.; DE OLIVEIRA, KLEBER T.; HAMBLIN, MICHAEL R.; DA SILVA, ROBERTO S.. Design, synthesis and photobiological activity of novel ruthenium phthalocyanine complexes. Inorganic Chemistry Communications, v. 99, p. 60-63, . (15/03746-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
NEGRI, Laísa Bonafim. Photobiomodulation and nitric oxide as strategies to potentiate the antitumor action of photodynamic therapy mediated by ruthenium-phthalocyanines: Chemical, biochemical and photobiological aspects. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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