Desenvolvimento de nanomateriais contendo IR780 para aplicação na terapia do cancro

• Autor(a) principal: Alves, Cátia Gomes
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/9860
• topic: Cancro; Micelas Direcionadas; Quimioterapia; Terapia Combinatória; Terapia Fototérmica; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Breast cancer is a leading cause of death among women. This reality is in part owed to the sub-optimal efficacy and non-specific toxicity of the currently available treatments. In this way, there is an urge need to develop innovative therapies for breast cancer. In the recent years, phototherapies mediated by nanomaterials have been showing promising results in cancer treatment. This type of therapy takes advantage from the ability of nanostructures to accumulate preferentially in the tumor zone. Afterwards, this site is irradiated with near infrared light (NIR) and nanomaterials upon interaction with NIR light, induce a temperature increase (photothermal therapy) or the formation of reactive oxygen species (photodynamic therapy), which can cause damage on cancer cells. Furthermore, nanostructures’ core can also accommodate chemotherapeutic drugs, enabling their application in cancer chemo-phototherapy. Some nanostructures can also emit fluorescence upon exposure to NIR light, thus being promising for imaging applications. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was synthesized and explored for the preparation of polymeric micelles aimed to be used for targeted breast cancer chemo-phototherapy. For such, Doxorubicin (chemotherapeutic agent, DOX) and IR780 (NIR-responsive photothermal agent, photosensitizer and imaging dye) were encapsulated in the micelles’ core. The results revealed that HA-based micelles (HPM) were able to successfully encapsulate IR780 (IR-HPM) and the IR780-DOX combination (IR/DOX-HPM). Furthermore, the encapsulation of IR780 in HPM improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential as well as its cytocompatibility. In the in vitro uptake studies, the fluorescence signals emitted by HPM were explored for cell imaging and the acquired data demonstrated that the nanostructures were preferentially internalized by breast cancer cells. These findings highlight the potential of these nanoformulations for CD44 targeting and cancer diagnosis. Moreover, IR-HPM alone did not induce any noticeable cytotoxicity to breast cancer cells. However, when this formulation was irradiated with NIR light a reduction on cancer cells’ viability was obtained. The combined effect of IR/DOX-HPM and NIR light further decreased cancer cells’ viability. Overall, based on the results obtained we can state that HPM are promising nanoplatforms for targeted chemo-phototherapy and imaging.