Photosensitization in membrane models and in neuronal cells (2021)
- Authors:
- Autor USP: GOMES, RAPHAEL DE AVILA NARCISO - IQ
- Unidade: IQ
- Sigla do Departamento: QFL
- DOI: 10.11606/D.46.2021.tde-26042022-083934
- Subjects: RUTÊNIO; TERAPIA FOTODINÂMICA; MEMBRANAS CELULARES; FOTOSSENSIBILIZAÇÃO EM ANIMAL; FOTOQUÍMICA
- Keywords: Células neuronais; Complexos de rutênio; DMMB; DMMB; Fotossensibilização; Lipid membranes; Membranas; Neuronal cells; Photodynamic therapy; Photosensitization; Ruthenium complexes; Terapia fotodinâmica
- Agências de fomento:
- Language: Inglês
- Abstract: Photodynamic therapy (PDT) is being extensively studied and tested to treat different types of diseases, such as cancer, leishmaniosis, malaria, among others. PDT usually comprises the use of photosensitizers, oxygen and light to increase the oxidative stress in cells and tissues. Preferred photosensitizers display: i) high absorption coefficient in the visible range of the light spectra; ii) high efficiency of triplet excited state generation with energy suitable to allow efficient energy transfer to form singlet oxygen; iii) physical-chemical and biochemical properties that allow interaction with important biological targets. Usually organic compounds, such as porphyrin or phenothiazinium derivatives, are used as photosensitizers (PS), but ruthenium complexes are also promising compounds to function as PDT PS. In this work the photodynamic effects of ruthenium photoactive complexes were evaluated in membrane small unilamellar vesicles (SUVs) and giant unilamellar vesicles (GUVs) and in a cellular model (Mouse Hippocampal Neuronal Cell Line - HT22). The phototoxicity of the complexes in HT22 cells were analysed, and the photochemical damage in the cell and mitochondria was observed by flow cytometry and microscopy. Experiments were also designed to compare its efficiency with an efficient phenothiazinium (dimethyl-methylene blue DMMB). The ruthenium complexes were able to damage the membranes of GUVs and SUVs and the damage efficiency does not seem to be related to the efficiency of singlet oxygen generation, but to membrane bonding. In HT22 cells Ru complexes were able to damage mitochondria. Damage could not be reverted by general anti-oxidant agents. The LD50 were calculated to be from 17 to 25 M from 8000 to 25000 cells, which implicates in intracellular concentrations of ~80pM/cell. DMMB also causes severe damage in mitochondria as indicated by mitochondria morphology, mitoSox staining, andlipid peroxidation. The LD50 were calculated to be 30 to 35 and 40 nM for incubations with 5000, 6000 and 8000 cells, respectively, which implicates in intracellular concentrations of ~2pM/cell. It is clear that DMMB is more efficient (~40 times) in terms of causing cell death (compared PS intracellular concentrations at the LD50), probably because for its higher tendency to bind more efficiently to membranes. We expect to have higher efficiency in Ru complexes with more lipophilic ligands
- Imprenta:
- Data da defesa: 30.06.2021
- Este periódico é de acesso aberto
- Este artigo NÃO é de acesso aberto
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ABNT
GOMES, Raphael de Avila Narciso. Photosensitization in membrane models and in neuronal cells. 2021. Dissertação (Mestrado) – Universidade de São Paulo, São Paulo, 2021. Disponível em: https://www.teses.usp.br/teses/disponiveis/46/46136/tde-26042022-083934/. Acesso em: 26 jan. 2026. -
APA
Gomes, R. de A. N. (2021). Photosensitization in membrane models and in neuronal cells (Dissertação (Mestrado). Universidade de São Paulo, São Paulo. Recuperado de https://www.teses.usp.br/teses/disponiveis/46/46136/tde-26042022-083934/ -
NLM
Gomes R de AN. Photosensitization in membrane models and in neuronal cells [Internet]. 2021 ;[citado 2026 jan. 26 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46136/tde-26042022-083934/ -
Vancouver
Gomes R de AN. Photosensitization in membrane models and in neuronal cells [Internet]. 2021 ;[citado 2026 jan. 26 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46136/tde-26042022-083934/
Informações sobre o DOI: 10.11606/D.46.2021.tde-26042022-083934 (Fonte: oaDOI API)
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