Development of a new drug delivery system for future application in cancer therapy

• Autor(a) principal: Gaspar, Vítor Manuel Abreu
• Data de Publicação: 2010
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/2308
• topic: Cancro - Terapia génica; Células cancerígenas - DNA plasmídico - Nanosistemas

During the past few decades gene therapy has become a promising alternative for the treatment of many incurable diseases such as cancer. This extremely complex disease possesses characteristics that make most of the generally used treatments rather ineffective. The research work presented in this thesis attempts to take advantage of novel non-viral gene therapeutic approaches based on plasmidic DNA and nanoparticulated systems that might provide the foundation for the development of a novel therapeutic treatment from the production to a real application in the everyday life of cancer patients. Hence the production of an expression vector that encodes for a tumor suppressor, p53 was promoted in recombinant organisms. Subsequently the different plasmid DNA isoforms were isolated and the supercoiled isoform, the one biologically active and with enhanced transfection efficiency was purified by affinity chromatography. Following this purification and recovery the development of novel nanoparticle systems that could deliver the exogenous DNA into the malignant cells was promoted. Nanoparticulated systems produced with chitosan demonstrated small size ranges and suitable properties for the encapsulation of plasmidic DNA. Additionally, transfection of eukaryotic neoplastic cells revealed the suitability of the nanocarrier as a novel delivery system of p53 expression vectors to cancer.