Development of ruthenium theranostic prodrugs for cancer therapy

Detalhes bibliográficos
Autor(a) principal: Lourenço, Maria Joana Ramos Lopes Ribeiro
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/61750
Resumo: Tese de mestrado, Química (Química), 2023, Universidade de Lisboa, Faculdade de Ciências
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spelling Development of ruthenium theranostic prodrugs for cancer therapyTeranósticosConjugados Ru(II)-SondaTerapia contra o cancroFluorescênciaTeses de mestrado - 2023Departamento de Química e BioquímicaTese de mestrado, Química (Química), 2023, Universidade de Lisboa, Faculdade de CiênciasCancer is a major public health problem and a leading cause of mortality worldwide. Despite the clinical success of various chemotherapeutic medications, these are usually not selective and thus frequently cause considerable harmful effects on tissues that are not malignant. Furthermore, late diagnosis leads to survival rates remaining low. In this work we aimed to address these limitations through the development of smart theranostic agents. Theranostics, combining therapy and diagnostic, are used for cancer therapy as their diagnostic agent enables the identification of tumors while the therapeutic agent is used for treatment. The structure of the theranostic agent planned in this work is based on a ruthenium complex that has previously shown to be very effective in vitro against several tumors, conjugated to a diagnostic agent with selective affinity for Bcl-2, which are overexpressed proteins in the cancer cells. This diagnostic agent is comprised of a targeting unit, which is responsible for the affinity, and a probe that allows for monitorization of the biodistribution and drug delivery. This extremely precise system is expected to remain inactive throughout distribution. However, the linker is expected to break when it reaches the target, enabling both the release of the ruthenium complex drug in its active form, and the activation of the probe. In this work, evaluation of two methods for the preparation of the targeting unit was performed; synthesis of the probe was achieved with high yields (60-90%) by two different routes; various methods of isolation were studied; derivatization of the probe was studied through two synthetic strategies. Regarding the therapeutic agent, five Ru(II) complexes were synthesized, of which one is a new complex; two new Ru(II)-Probe conjugates were synthesized; the new complex and the conjugates were characterized by NMR, UV-Vis and FTIR; the stability of the new complex and both conjugates was evaluated over 24 h by UV-Vis in DMSO and 95:5 DMEM/DMSO solutions.Coelho, Jaime Alfredo da SilvaMorais, Tânia Sofia Ferreira, 1980-Repositório da Universidade de LisboaLourenço, Maria Joana Ramos Lopes Ribeiro2024-01-13T13:09:25Z202320232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/61750engmetadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-15T01:19:11Zoai:repositorio.ul.pt:10451/61750Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:44:37.482205Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Development of ruthenium theranostic prodrugs for cancer therapy
title Development of ruthenium theranostic prodrugs for cancer therapy
spellingShingle Development of ruthenium theranostic prodrugs for cancer therapy
Lourenço, Maria Joana Ramos Lopes Ribeiro
Teranósticos
Conjugados Ru(II)-Sonda
Terapia contra o cancro
Fluorescência
Teses de mestrado - 2023
Departamento de Química e Bioquímica
title_short Development of ruthenium theranostic prodrugs for cancer therapy
title_full Development of ruthenium theranostic prodrugs for cancer therapy
title_fullStr Development of ruthenium theranostic prodrugs for cancer therapy
title_full_unstemmed Development of ruthenium theranostic prodrugs for cancer therapy
title_sort Development of ruthenium theranostic prodrugs for cancer therapy
author Lourenço, Maria Joana Ramos Lopes Ribeiro
author_facet Lourenço, Maria Joana Ramos Lopes Ribeiro
author_role author
dc.contributor.none.fl_str_mv Coelho, Jaime Alfredo da Silva
Morais, Tânia Sofia Ferreira, 1980-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Lourenço, Maria Joana Ramos Lopes Ribeiro
dc.subject.por.fl_str_mv Teranósticos
Conjugados Ru(II)-Sonda
Terapia contra o cancro
Fluorescência
Teses de mestrado - 2023
Departamento de Química e Bioquímica
topic Teranósticos
Conjugados Ru(II)-Sonda
Terapia contra o cancro
Fluorescência
Teses de mestrado - 2023
Departamento de Química e Bioquímica
description Tese de mestrado, Química (Química), 2023, Universidade de Lisboa, Faculdade de Ciências
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023-01-01T00:00:00Z
2024-01-13T13:09:25Z
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