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Effect of photobiomodulation as synergistic addendum on photocytotoxicity of ruthenium-phthalocyanine compounds as nitric oxide and singlet oxygen producers: in vitro biochemical evaluation in two- and three-dimensional (3D) tumor cell lines


It is known from previous studies that nitric oxide (NO) is a biological messenger of physiological and anticancer processes, and its functions depend on its concentration and place of action. These characteristics have motivated the search for a clinical application of compounds that can, in a controlled way, release NO. Among this possibility, the group led by prof. Roberto S. da Silva (FCFRP-USP) has been developing, in partnership with Harvard University and the University of California, systems that can be applied to photodynamic therapy (PDT) based on ruthenium compounds. In this context, synergistic effect between NO and reactive oxygen species (ROS) are applied in the modulation of cancer cell death. These studies are aimed at an upgrade in PDT and developing a new class of metal-based drugs. In this context, the project proposed here contributes to this development. The project focuses on the study of the biological effects of the presence of nitric oxide, as well as the effect of the presence of singlet oxygen in the regulation of tumor cell signaling pathways with a special focus on the induction of death. In anticipation of in vivo application, results in two-dimensional and three-dimensional (3D) cell models will be used. Three-dimensional culture systems are an important tool for molecular understanding and cellular processes of compound / drug induced cytotoxicity. 3D culture is being developed as one of the most advanced in vitro models for cell organization capable of modulating molecular gradients of living tissues such as oxygen, nutrients, metabolites and signaling molecules with the special advantage of reducing the need for animals for this analysis. The compounds used in this study absorb irradiation in the therapeutic window region and provide photoinduced electron transfer, which in the presence of ruthenium nitrosyl complexes release NO. The biochemical mechanisms related to the interaction of the ruthenium-cell complex, as well as the identification, activation and regulation of cell death signaling pathways will be evaluated. For this, the following analysis tools will be used: proteomics, Western blotting, confocal microscopy, flow cytometry and gene manipulation techniques, ie silencing / deletion of genes of interest. This study is expected to more briefly predict the role of ruthenium-nitrosyl complexes as a potential drug in the three-dimensional cancer cell line system. (AU)

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Scientific publications (12)
(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)
CASTRO, KELLY A. D. F.; PRANDINI, JULIANA A.; BIAZZOTTO, JULIANA CRISTINA; TOME, JOAO P. C.; DA SILVA, ROBERTO S. S.; LOURENCO, LEANDRO M. O.. The Surprisingly Positive Effect of Zinc-Phthalocyanines With High Photodynamic Therapy Efficacy of Melanoma Cancer. RONTIERS IN CHEMISTR, v. 10, p. 9-pg., . (16/12707-0, 13/07937-8, 19/19448-8)
PRANDINI, JULIANA A.; CASTRO, KELLY A. D. F.; BIAZZOTTO, JULIANA C.; BRANCINI, GUILHERME T. P.; TOME, JOAO P. C.; LOURENCO, LEANDRO M. O.; BRAGA, GILBERTO U. L.; DA SILVA, ROBERTO S.. Thiopyridinium phthalocyanine for improved photodynamic efficiency against pathogenic fungi. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 231, p. 8-pg., . (16/11386-5, 19/19448-8)
SILVA, LETICIA B.; CASTRO, KELLY A. D. F.; BOTTEON, CAROLINE E. A.; OLIVEIRA, CRISTIANO L. P.; DA SILVA, ROBERTO S.; MARCATO, PRISCYLA D.. Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 9, . (19/19448-8, 14/50928-2, 18/13465-5, 16/12707-0)
CASTRO, KELLY A. D. F.; RAMOS, LOYANNE; MESQUITA, MARIANA; BIAZZOTTO, JULIANA CRISTINA; MOURA, NUNO M. M.; MENDES, RICARDO F.; PAZ, FILIPE A. ALMEIDA; TOME, AUGUSTO C.; CAVALEIRO, JOSE A. S.; SIMOES, MARIO M. Q.; et al. Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line. ACS APPLIED BIO MATERIALS, v. 4, n. 6, p. 4925-4935, . (19/19448-8)
PAVANELLI, ANDRE L. S.; MAXIMO, LEANDRO N. C.; DA SILVA, ROBERTO S.; BORISSEVITCH, IOURI E.. Effect of Serum Albumin on Porphyrin-Quantum Dot Complex Formation, Characteristics and Spectroscopic Analysis. NANOMATERIALS, v. 11, n. 7, . (19/19448-8, 16/12707-0)
MACEDO, LUCYANO J. A.; RODRIGUES, FERNANDO P.; HASSAN, AYAZ; MAXIMO, LEANDRO N. C.; ZOBI, FABIO; DA SILVA, ROBERTO S.; CRESPILHO, FRANK N.. Non-destructive molecular FTIR spectromicroscopy for real time assessment of redox metallodrugs. ANALYTICAL METHODS, . (19/15333-1, 17/20493-2, 18/22214-6, 19/12053-8, 19/19448-8)
CASTRO, KELLY A. D. F.; BIAZZOTTO, JULIANA CRISTINA; TOME, JOAO P. C.; DA SILVA, ROBERTO S.; LOURENCO, LEANDRO M. O.. In vitro anti-tumoral activity of two versatile cationic porphyrins on melanoma cells. JOURNAL OF PORPHYRINS AND PHTHALOCYANINES, v. 27, n. 1, p. 7-pg., . (22/15336-3, 19/19448-8)
RIOS, RAFAELLA REBECCHI; SOUSA RODRIGUES, PHAMILLA GRACIELLI; BIAZZOTTO, JULIANA C.; GALEMBECK, SERGIO EMANUEL; DA SILVA, ROBERTO SANTANA. Effects of First-Coordination Sphere and Buffers on the Nitrosyl-Nitrite Conversion Rate in Ru(II) Complexes. European Journal of Inorganic Chemistry, v. 2022, n. 30, p. 8-pg., . (19/19448-8)
MARTINS, TASSIA JOI; NEGRI, LAISA BONAFIM; PERNOMIAN, LAENA; FAIAL, KELSON DO CARMO FREITAS; XUE, CONGCONG; AKHIMIE, REGINA N.; HAMBLIN, MICHAEL R.; TURRO, CLAUDIA; DA SILVA, ROBERTO S.. The Influence of Some Axial Ligands on Ruthenium-Phthalocyanine Complexes: Chemical, Photochemical, and Photobiological Properties. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 7, . (19/19448-8)
MOURA, NUNO M. M.; SERRA, VANDA VAZ; BASTOS, ALEXANDRE; BIAZOTTO, JULIANA C.; CASTRO, KELLY A. D. F.; FAUSTINO, MARIA AMPARO F.; LODEIRO, CARLOS; DA SILVA, ROBERTO S.; NEVES, MARIA DA GRACA P. M. S.. New Bis-Cyclometalated Iridium(III) Complexes with beta-Substituted Porphyrin-Arylbipyridine as the Ancillary Ligand: Electrochemical and Photophysical Insights. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 14, p. 19-pg., . (19/19448-8)
GASPARI, ANA P. S.; DA SILVA, ROBERTO SANTANA; CARNEIRO, ZUMIRA A.; DE CARVALHO, MARCELO RODRIGUES; CARVALHO, IVONE; PERNOMIAN, LAENA; FERREIRA, LUCIMARA P.; RAMOS, LOYANNE C. B.; DE SOUZA, GABRIEL AGUIAR; FORMIGA, ANDRE L. B.. Improving Cytotoxicity Against Breast Cancer Cells by Using Mixed-Ligand Ruthenium(II) Complexes of 2,2'-Bipyridine, Amino Acid, and Nitric Oxide Derivatives as Potential Anticancer Agents. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 21, n. 12, p. 1602-1611, . (13/22127-2, 19/19448-8)
CASTRO, KELLY A. D. F.; MOURA, NUNO M. M.; SIMOES, MARIO M. Q.; MESQUITA, MARIANA M. Q.; RAMOS, LOYANNE C. B.; BIAZZOTTO, JULIANA C. C.; CAVALEIRO, JOSE A. S.; FAUSTINO, M. AMPARO F.; NEVES, MARIA GRACA P. M. S.; DA SILVA, ROBERTO S. S.. A Comparative Evaluation of the Photosensitizing Efficiency of Porphyrins, Chlorins and Isobacteriochlorins toward Melanoma Cancer Cells. Molecules, v. 28, n. 12, p. 15-pg., . (22/15336-3, 19/19448-8)

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