Steroid-BODIPY theranostics: Receptor-mediated cell uptake and applications in cancer Diagnostics and therapy

• Autor(a) principal: Amendoeira, Ana Filipa Patrício
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/103277
• topic: Cancer; steroid-BODIPY conjugates; cellular uptake; Photodynamic Therapy; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Cancer is still one of the leading cause of death worldwide despite the intensive investigation of the disease mechanisms and the development of new therapeutic approaches. Therefore, it is urgent to develop novel diagnostic and treatment platforms more selective and sparing healthy cells and overcoming resistance of cancer cells. Here, we report the study of estradiol-, testosterone- and nortestosterone derivates conjugated to BODIPY dye as a potential multi-modality theranostic agents (positron emission tomography (PET)/ fluorescence and photodynamic therapy (PDT)). Cellular uptake assays were performed in relevant breast and prostate cancer cells, as well as in normal fibroblasts, using fluorescence microscopy, in order to evaluate the trafficking pathways. Results showed a non-specific internalization of conjugates in cancer and normal cells, suggesting an energy-dependent cellular uptake through caveolae-mediated endocytosis. 2D co-cultures demonstrated that the conjugates are more specific for cancer cells. Cell viability assays showed that BODIPY conjugates are non-toxic for cancer and normal cells. In contrast, upon visible light irradiation a severe cell death effect was observed. Results demonstrated that EE2-C8 and HA-4198 steroid-BODIPY conjugates are potential photosensitizers for PDT against breast and prostate cancer cells. Future work are needed to gain more clues into the mechanism of action induced by these platforms after PDT.