Development of multifunctional IR780 based nanomaterials for cancer therapy

• Autor(a) principal: Leitao, Miguel Marques
• 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/10400.6/10551
• topic: Cancro; Ir780; Óxido de Grafeno; Revestimentos Zwiteriónicos; Terapia Fototérmica; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Breast cancer is a common cause of death among women. This scenario is in part explained by the limitations presented by the treatments currently used in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects. In this way, it is necessary to develop innovative strategies that propel the breast cancer therapy efficacy. Among the different therapeutic strategies under investigation, cancer photothermal therapy mediated by nanomaterials has been showing promising results. This type of therapy takes advantage from the nanomaterials’ physico-chemical properties, that enable their tumor accumulation. Subsequently, the tumor zone is irradiated with Near Infrared (NIR; 750-1000 nm) light and the tumor-homed nanomaterials absorb this energy, releasing it as heat that causes damage to cancer cells. From the plethora of nanomaterials with potential to be applied in cancer photothermal therapy, Graphene Oxide (GO) is a promising candidate due to its NIR absorption and loading capacity. However, as-synthesized GO lacks colloidal stability, i.e., it precipitates when in contact with biological fluids. On the other hand, GO displays a modest photothermal capacity, requiring the use of high doses or intense radiation to achieve the desired therapeutic effect. In the work developed during my MSc, GO was functionalized with an amphiphilic polymer containing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) brushes and was loaded with IR780 (a NIR photoabsorber), for the first time, to improve its colloidal stability and phototherapeutic capacity, respectively. The obtained results revealed that the SBMA-functionalized GO displays a suitable size distribution, neutral surface charge and an appropriate cytocompatibility. Furthermore, the SBMA-functionalized GO exhibited an improved colloidal stability in biological relevant media (at least up to 48 h), while GO without SBMA functionalization promptly precipitated in the same conditions. By loading IR780 into the SBMA-functionalized GO, its NIR absorption increased by 2.7-fold (at 808 nm), leading to a 1.2-times higher photothermal heating. In in vitro cell studies, the conjugation of NIR irradiation with SBMA-functionalized GO could reduce breast cancer cells’ viability to 73 %. In stark contrast, by combining IR780 loaded SBMA-functionalized GO and NIR radiation, the cancer cells’ viability decreased to 20 %. Overall, the IR780 loaded SBMA-functionalized GO nanomaterials have promising properties for application in breast cancer phototherapy.