Browsing by Author "Melo, Bruna Daniela Lopes"
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- Development of multifunctional graphene oxide based nanomaterials for cancer therapyPublication . Melo, Bruna Daniela Lopes; Diogo, Duarte Miguel de Melo; Correia, Ilídio Joaquim Sobreira; Sousa, Ana Rita LimaBreast cancer remains as one of the deadliest diseases affecting the worldwide population. The high mortality rate exhibited by this disease can be attributed to the limitations of the treatments currently in use in the clinic (e.g. radiotherapy, chemotherapy), which display a low therapeutic efficacy and induce adverse side effects in patients. Therefore, there is an urgent demand for innovative therapeutic approaches that can enhance breast cancer survival rates. Recently, nanomaterials’ mediated Photothermal Therapy (PTT) has been showing promising results for cancer treatment. This therapeutic modality employs nanostructures that, due to their specific set of physicochemical characteristics, can accumulate at the tumor site. Afterwards, this zone is irradiated with Near Infrared (NIR) light and the tumor-homed nanomaterials induce a local temperature increase (hyperthermia) that can induce damage to cancer cells. Among the several nanomaterials with potential for cancer PTT, Graphene Oxide (GO) has been extensively investigated due to its absorption in the NIR. After interacting with this radiation, GO produces a temperature increase that can cause damage to cancer cells. In addition, this nanomaterial has an aromatic matrix that can be used to encapsulate a wide variety of compounds, thus having a great versatility. However, the direct application of GO in cancer PTT is limited by two factors: i) the low colloidal stability of GO, which causes its precipitation in biological fluids, and ii) the poor photothermal capacity of GO, which leads to the use of high doses/intense radiation in order to achieve an adequate therapeutic effect. In this MSc research work, GO was functionalized with an albumin based amphiphilic coating containing Sulfobetaine Methacrylate (SBMA) brushes (SBMA-g-BSA) and was loaded with IR780, with the intent to improve its colloidal stability and photothermal capacity, respectively. The results revealed that GO functionalized with SBMA-g-BSA (SBMA-BSA/GO) presents an adequate size distribution and cytocompatibility for cancer-related applications. When in contact with biologically relevant media, the size of the SBMA-functionalized GO derivatives only increased by 8 % after 48 h. In the same condition and period, the non-SBMA functionalized GO (BSA coated GO) suffered a 31 % increase in its size. By loading IR780 into SBMA-BSA/GO (IR/SBMA-BSA/GO), the nanomaterials’ NIR absorption increased by 5.6-fold. In this way, the IR/SBMA-BSA/GO could produce a up to 2-times higher photoinduced heat than SBMA-BSA/GO. In in vitro cell studies, the combination of NIR light with SBMA-BSA/GO did not induce photocytotoxicity on breast cancer cells. In stark contrast, the interaction of IR/SBMA-BSA/GO with NIR light caused the ablation of cancer cells (cell viability < 2 %). Overall, IR/SBMA-BSA/GO displays a greatly improved colloidal stability and phototherapeutic capacity, being a promising hybrid nanomaterial for application in the PTT of breast cancer cells.