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Nanozimas de Ruténio para a terapia seletiva do cancro metastático

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Resumo(s)

Cancer is one of the principal global health issues, with about 90% of deaths caused by it being associated with the development of metastases. In the last decades, ruthenium compounds have emerged as promising anticancer agents. The Faculty’s of Science of University of Lisbon (Bio)Organometallic Chemistry group has been developing RuCp (Cp = η5-cyclopentadienyl) complexes that showed high cytotoxicity in different cancer types. At the same time, nanozymes, nanomaterials with catalytic activity similar to that of enzymes, offer the advantages of low cost and high stability. Among various nanozymes, ruthenium nanoparticles (RuNP) possess excellent peroxidase-like activity that can be used to covert the excess of H2O2 present in cancer cells into reactive oxygen species, causing the cell’s death. This work aimed to develop a potential therapeutic system by combining cytotoxicity of RuCp complexes with peroxidise-like catalytic activity exhibited by RuNp, aiming to explore a dual-action approach to target tumour cells. In the course of this work, two RuCp complexes that had already shown promising results in vivo and in vitro ([RuCp(PPh3)(2,2´-bipy)][CF3SO3] e [RuCp(PPh3)(bopy)][CF3SO3], where 2,2´-bipy = 2,2´- bipyridine e bopy = 2-benzoylpyridine) were synthesized, characterized, and used to impregnate RuNP, achieving a higher degree of impregnation for [RuCp(PPh3)(bopy)][CF3SO3], in comparison to [RuCp(PPh3)(2,2´-bipy)][CF3SO3]. The catalytic activity of RuNP and of the RuNP+RuCp systems was evaluated in dimethyl sulfoxide and in aqueous media at pH 7.4 and 6.8. Among other findings, it was observed that the catalytic activity of the RuNP+RuCp systems increased with decreasing of a pH value. Thus, in this study, two RuNP systems functionalized with RuCp complexes were obtained. The RuCp complexes enhanced the peroxidase-like activity of these nanoparticles at pH = 6,8, which is very advantageous for their action in the acidic tumour environment.

Descrição

Tese de mestrado, Química (Química), 2025, Universidade de Lisboa, Faculdade de Ciências

Palavras-chave

Metastatic Cancer Organometallic complexes RuCp Nanozymes Reactive oxygen species (ROS)

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