From the green chlorophyll in plants and algae that we depend upon to transform sunlight into useful energy, to the red heme that carries oxygen to the cells in our bodies, porphyrins are the colors of life. It is not surprising then, that porphyrins have been actively interrogated as tools for diverse applications to improve biotechnology and medicine. With the goal of improving cancer therapy and diagnosis in mind, this thesis examines new modular porphyrin architectures. These constructs have interesting properties that extend beyond their originally intended use as phototherapeutic agents. In Chapter 1, a comprehensive background on porphyrin-based activatable photosensitizers is presented. In Chapter 2, porphyrin singlet oxygen and fluorescence quenching is examined in a model system with respect to Förster theory. Chapter 3 examines a new DNA responsive molecular beacon that was quenched using multiple quenching moieties and its application for nanoparticle aggregation. Chapter 4 describes extremely self-quenched nanovesicles formed from porphyrin-lipid conjugates that displayed a number of desirable properties for nanomedicine applications. Chapter 5 presents a brief discussion and some potential future directions of the research. It is my hope that the data presented in this thesis set the stage for new porphyrin-based approaches to make a translational impact in the battle against cancer and other diseases.

From the green chlorophyll in plants and algae that we depend upon to transform sunlight into useful energy, to the red heme that carries oxygen to the cells in our bodies, porphyrins are the colors of life. It is not surprising then, that porphyrins have been actively interrogated as tools for diverse applications to improve biotechnology and medicine. With the goal of improving cancer therapy and diagnosis in mind, this thesis examines new modular porphyrin architectures. These constructs have interesting properties that extend beyond their originally intended use as phototherapeutic agents. In Chapter 1, a comprehensive background on porphyrin-based activatable photosensitizers is presented. In Chapter 2, porphyrin singlet oxygen and fluorescence quenching is examined in a model system with respect to Förster theory. Chapter 3 examines a new DNA responsive molecular beacon that was quenched using multiple quenching moieties and its application for nanoparticle aggregation. Chapter 4 describes extremely self-quenched nanovesicles formed from porphyrin-lipid conjugates that displayed a number of desirable properties for nanomedicine applications. Chapter 5 presents a brief discussion and some potential future directions of the research. It is my hope that the data presented in this thesis set the stage for new porphyrin-based approaches to make a translational impact in the battle against cancer and other diseases.

Este projeto teve como finalidade construir uma fonte de luz baseada em lâmpadas halógenas que apresentasse características técnicas adequadas para aplicações em fotobiologia e fotomedicina, versátil e comercialmente viável. Foram analisadas as características de diferentes lâmpadas halógenas e realizados os experimentos com duas lâmpadas escolhidas, das quais utilizamos a lâmpada de menor divergência luminosa. Foi analisado também o material do corpo da fonte, com relação a características de aquecimento e peso, sendo escolhido um corpo de alumínio produzido industrialmente. Foram avaliadas as características ópticas das lentes, sendo escolhidas as lentes de vidro utilizadas em retroprojetores. Foram analisados os materiais e a construção de filtros térmicos para diminuir o aquecimento do objeto sob irradiação, sendo que escolhemos construir um filtro térmico próprio, que utiliza a água como absorvedor de calor. Medimos e avaliamos as características: espectrais, térmicas, a potência radiante (irradiância) e sua distribuição espacial de três protótipos, onde cada um recebeu modificações de modo a torná-los mais adequados para aplicações na fotoquimeoterapia. Foram também realizados testes preliminares de fotocitotoxicidade do protótipo final com o composto fotossensibilizador de nome comercial Photogem® aplicado em células tumorais de adenocarcinoma de colo retal humano (HT29), cujo resultado foi a ativação do composto fotossensibilizador e indução da morte celular. / The aim of this work was to produce a light source based in halogen lamps. This source should have appropriated technical characteristic for application in photobiology and photomedicine, it has easy operation and be commercially viable. The characteristics of different halogen lamps were evaluated and the lamp of smaller luminous divergence was chosen. We also have evaluated the material of the source holder, especially heating characteristics and weight; finally we chose an aluminum holder. Then, the lenses optical characteristics were studied, and we decided that the glass lenses used in projectors were the best. The materials and the construction of thermal filters were evaluated in order to reduce the heating of the object under irradiation, and we preferred to construct a thermal filter, that uses water as an heat absorber. The spectral and thermal characteristics, the radiant power (irradiance) and its space distribution of three prototypes were measured and evaluated, each one received modifications to become more appropriated to applications in photochemotherapy. We also made preliminaries tests of photocytotoxicity and the final prototype was used with the photosensitizer (Photogem®) in human colon carcinoma cell lines HT-29, resulting in the photosensitizer activation, that induced cellular death.

Este projeto teve como finalidade construir uma fonte de luz baseada em lâmpadas halógenas que apresentasse características técnicas adequadas para aplicações em fotobiologia e fotomedicina, versátil e comercialmente viável. Foram analisadas as características de diferentes lâmpadas halógenas e realizados os experimentos com duas lâmpadas escolhidas, das quais utilizamos a lâmpada de menor divergência luminosa. Foi analisado também o material do corpo da fonte, com relação a características de aquecimento e peso, sendo escolhido um corpo de alumínio produzido industrialmente. Foram avaliadas as características ópticas das lentes, sendo escolhidas as lentes de vidro utilizadas em retroprojetores. Foram analisados os materiais e a construção de filtros térmicos para diminuir o aquecimento do objeto sob irradiação, sendo que escolhemos construir um filtro térmico próprio, que utiliza a água como absorvedor de calor. Medimos e avaliamos as características: espectrais, térmicas, a potência radiante (irradiância) e sua distribuição espacial de três protótipos, onde cada um recebeu modificações de modo a torná-los mais adequados para aplicações na fotoquimeoterapia. Foram também realizados testes preliminares de fotocitotoxicidade do protótipo final com o composto fotossensibilizador de nome comercial Photogem® aplicado em células tumorais de adenocarcinoma de colo retal humano (HT29), cujo resultado foi a ativação do composto fotossensibilizador e indução da morte celular. / The aim of this work was to produce a light source based in halogen lamps. This source should have appropriated technical characteristic for application in photobiology and photomedicine, it has easy operation and be commercially viable. The characteristics of different halogen lamps were evaluated and the lamp of smaller luminous divergence was chosen. We also have evaluated the material of the source holder, especially heating characteristics and weight; finally we chose an aluminum holder. Then, the lenses optical characteristics were studied, and we decided that the glass lenses used in projectors were the best. The materials and the construction of thermal filters were evaluated in order to reduce the heating of the object under irradiation, and we preferred to construct a thermal filter, that uses water as an heat absorber. The spectral and thermal characteristics, the radiant power (irradiance) and its space distribution of three prototypes were measured and evaluated, each one received modifications to become more appropriated to applications in photochemotherapy. We also made preliminaries tests of photocytotoxicity and the final prototype was used with the photosensitizer (Photogem®) in human colon carcinoma cell lines HT-29, resulting in the photosensitizer activation, that induced cellular death.