Potential effects of nanostructured protoporphyrin IX-mediated photodynamic therapy in different types of cancer

• Ano de defesa: 2020
• Autor(a) principal: Leite, Ilaiáli Souza
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Nanotechnology; Nanotecnologia; Photodynamic therapy; Protoporfirina IX; Protoporphyrin IX; Terapia fotodinâmica
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/76/76132/tde-29092020-113611/

Light-photoactive substances interactions assessment to promote cell death as therapeutic outcome was initially introduced by Oscar Raab in the late 1800s. Since then, the forementioned technique - photodynamic therapy (PDT) - has been evaluated to treat a wide range of diseases. Cancer, a collection of related diseases, is among the leading causes of mortality worldwide and has been widely evaluated in research and clinical trials using PDT over the past 35 years. Although it may be prescribed for precancerous lesions treatment and some specific types of cancer, its effectiveness is limited by the ineffective photosensitizer buildup at the treatment site. Nanotechnology has addressed the problem of drug delivery through the development of different nanostructured platforms capable of increasing several pharmacological properties of molecules, such as their solubility and their circulating half-life. The association of nanotechnology´s potential to improve photosensitizer delivery to target tissues with the oxidative damage of PDT to induce cell death has emerged as a promising prospect for optimizing cancer treatment. In this study, we propose to evaluate the potential of redox- responsive silica nanoparticles and membrane fusogenic liposomes (MFLs) carrying protoporphyrin IX (PpIX) as the selected photosensitizer for melanoma, non-melanoma and breast cancer treatment using PDT in vitro. Studies evaluating the impact of different solvents on the free and nanostructured PpIX photostability, the nanoparticles and MFLs internalization, phototoxicity and reactive oxygen species (ROS) were carried out, showing that, despite the aggregation, the molecules and nanoparticles are internalized in sufficient quantity to promote massive damage to cell viability when irradiated with 630 nm.