Development of silica-coated gold nanoclusters for cancer therapy

• Autor(a) principal: Fernandes, Natanael Filipe Ferreira
• 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/10400.6/10806
• topic: Cancro; Glutationa; Nanoagregados; Nanopartículas de Ouro Com Revestimento de Sílica; Terapia Fototérmica; Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica

Cancer is one of the leading causes of death worldwide. Currently, the conventional treatments used in the clinic such as surgery, radiotherapy, and chemotherapy have a low therapeutic efficiency and adverse side effects on patients. This reality has propelled researchers to develop new and more effective therapeutic approaches such as immunotherapy, gene therapy, and hyperthermia. In the area of hyperthermia, the application of nanomaterials to mediate a photothermal effect (i.e., heat production in response to a light stimulus) and the consequent death of cancer cells has been the subject of several studies conducted by researchers and health professionals. Among the different types of nanoparticles developed up to date, gold nanoparticles coated with mesoporous silica (AuMSS) present excellent physical, chemical, and biological properties to be applied as photothermal agents and drug carriers. However, the application of spherical gold nanoparticles in the photothermic therapy of cancer is hampered by their low absorption in the near infrared (NIR) region. The work plan developed in this MSc dissertation aimed to produce and optimize the synthesis of AuMSS, composed of a core of gold nanospheres nanocluster, with an ideal morphology that is able to increase their absorption in the NIR region. With the increment of their absorption in the NIR region, allow them to produce an increase of temperature in the tumor tissues and, consequently, to be used as phototherapeutic agents. The obtained results revealed that the aggregation of gold nanospheres mediated by glutathione (GSH) was successful and the nanomaterials exhibited an uniform morphology with several gold nuclei and a well-defined silica coating. The optimization of the clustering of gold nanospheres allowed to improve their photothermal capacity, inducing changes in their absorption spectra, particularly, in the NIR region, as already expected. In the in vitro tests, all the formulations demonstrated to be biocompatible with both healthy (fibroblasts) and carcinogenic (cervical cancer) cells even when maximum concentrations of µ200 g/mL were used. Finally, the photothermic effect mediated by AuMSS nanoclusters effectively induced the death of cervical cancer cells. In summary, the obtained results confirm the potential of the AuMSSs to be applied in cancer therapy, where in the near future they canceragnostic agents, i.e. drug delivery and imaging agents.