Desenvolvimento e Funcionalização de Nanopartículas de Ouro com Revestimento de Sílica para Aplicação na Terapia do Cancro

• Autor(a) principal: Jacinto, Telma Maria Andrade
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/10160
• topic: Cancro; Ha; Nanopartículas de Ouro Com Revestimento de Sílica; Terapia Fototérmica; Tpgs; Domínio/Área Científica::Ciências Naturais::Ciências Químicas

Cancer is one of the leading causes of death in the worldwide population and recent data indicates that its incidence will continue to increase in the next years. On the other hand, the traditional treatments such as surgery, radiotherapy, and chemotherapy have low therapeutic efficacies and induce systemic toxicity. Such have prompted the development of new therapeutic approaches for cancer. In this area, the application of nanomaterials to mediate a photothermal effect (i.e. heat generation upon light irradiation) and consequently induce the death of cancer cells has gained a considerable recognition by researchers and health professionals. Among the various types of nanoparticles developed until now, gold coremesoporous silica coated nanoparticles (AuMSS) have excellent physicochemical and biological properties, which allow their application as photothermal agents and drug carriers. However, the application of these nanoparticles in cancer therapy is hindered by their reduced blood circulation time and poor specificity to the tumor tissue. Thus, the present dissertation aimed to develop a new surface functionalization for the rodshaped AuMSS nanoparticles based on biofunctional polymers, in order to increase its blood circulation time, internalization by the cancer cells, and ultimately increase the therapeutic effect. For this purpose, the rod-shaped AuMSS were chemically modified with different ratios (1:1 and 4:1) of D-a-Tocopherol polyethylene glycol 1000 succinate (TPGS) and Hyaluronic Acid (HA). HA was selected due to its specificity towards the CD44 receptors that are overexpressed in the cancer cells’ membrane. On the other hand, TPGS owing to its amphiphilic nature is able to increase the nanomaterials solubility, and consequently its colloidal stability that enhances the blood circulation time. The obtained results showed that the rod-shaped AuMSS’ functionalization neutralized the nanoparticles’ surface charge, from -28 ± 10 mV to -3 ± 5 mV and 11 ± 2 mV for AuMSS-TPGSHA (1:1) and (4:1), respectively, without compromising the nanomaterials’ size distribution or photothermal capacity. Moreover, the success of the polymers grafting to the nanoparticles was confirmed by Fourier Transform Infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). In vitro assays demonstrated the biocompatibility of all formulations at concentrations up to 200 µg / mL in both healthy (fibroblast) and cancerous (cervical cancer) cells. However, the functionalization with TPGS and HA has improved the nanomaterials’ hemocompatibility as well as their selectivity towards cervical cancer cells. Finally, the photothermal effect mediated by the rod-shaped AuMSS effectively induced the death of the cancer cells In summary, the results presented in this dissertation confirm the successful functionalization of the AuMSS with the TPGS and HA. Additionally, the AuMSSs’ potential to be applied in cancer photothermal therapy was also demonstrated.