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- Injectable hydrogels incorporating IR780-based nanostructures for photo-responsive anticancer applicationsPublication . Urbano, Carolina Dias; Diogo, Duarte Miguel de Melo; Correia, Ilídio Joaquim Sobreira; Melo, Bruna Daniela LopesBreast cancer represents one of the most challenging oncological issues nowadays. The persistently high mortality rates associated with this type of cancer are primarily attributed to the limited effectiveness of conventional clinical treatments such as surgery, radiotherapy, chemotherapy and immunotherapy. Despite their widespread use, these conventional therapies also induce side effects. Considering the conventional treatments’ aggressive issues, current studies are focusing on developing more precise therapeutic approaches to maximize the therapeutic effect on the tumor, while minimizing damage to healthy tissues. To address these limitations, the application of nanomaterials for cancer chemo-photothermal/photodynamic therapy is emerging. In this combined therapy, chemotherapeutic agents and molecules responsive to Near infrared (NIR) light are co-encapsulated into nanomaterials. After the tumor uptake of the nanoplatforms, these are exposed to NIR light, generating heat and/or reactive oxygen species that can synergize with the chemotherapeutic drugs for destroying cancer cells. However, it has been revealed that only a small percentage of the intravenously administered nanoparticles reaches the tumor site, limiting the therapeutic capacity of this combinatorial approach. Therefore, it is critical to overcome the limitations associated with the intravenous administration of nanoparticles. In this regard, injectable in situ forming hydrogels are gaining popularity for performing the direct delivery of nanomaterials into the tumor site. Once intratumorally injected, these macroscale formulations must achieve in situ gelation at the malignant site. This sol-gel transition can occur through chemical and/or physical crosslinking cues. As importantly, the hydrogels’ in situ formation must occur under mimetic physiologically conditions, and ideally, without the need of catalysts or initiators. When designing injectable in situ forming hydrogels, significant attention has also been given to the use of natural polymers due to their inherent biocompatibility, biodegradability and environmental sustainability. In this Master’s degree dissertation workplan, an injectable dual-crosslinked natural polymer-based hydrogel was assembled by combining Chitosan and Agarose, due to their ability to achieve a thermo-sensitive in situ gelation by electrostatic interactions and hydrogen bonding. This advanced hydrogel formulation was laden with nanoparticles prepared with a Sulfobetaine methacrylate-Bovine serum albumin conjugate, that were loaded with IR780 (photothermal/photodynamic agent) and Resveratrol (natural compound with chemotherapeutic activity), for being explored in cancer chemo-photothermal/photodynamic therapy. The data obtained showed that the nanoparticle-hydrogel complex exhibited injectability, in situ gelation capacity, suitable degradability/swelling and good photothermal capacity. The in vitro cell-based studies revealed that the nanocomposite hydrogel presented a good cytocompatibility. As importantly, the developed nanoparticle-incorporating hydrogel could generate a chemo-photothermal/photodynamic effect, under NIR laser irradiation, that reduced the breast cancer cells’ viability to just ≈ 30%. In summary, the injectable thermo-responsive Chitosan-Agarose in situ forming hydrogel incorporating Sulfobetaine methacrylate-Bovine serum albumin nanoparticles loaded with IR780 and Resveratrol is a promising platform for breast cancer chemo-photothermal/photodynamic therapy.