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Browsing FC - DQ | Documentos por Auto-Depósito by Author "Alves, Cátia"
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- Combining Photothermal‐Photodynamic Therapy Mediated by Nanomaterials with Immune Checkpoint Blockade for Metastatic Cancer Treatment and Creation of Immune MemoryPublication . Sousa, Rita Lima; Melo, Bruna L.; Alves, Cátia; Moreira, André; Mendonça, António; Correia, I.J.; Diogo, Duarte de MeloThe pursuit of effective treatments for metastatic cancer is still one of the most intensive areas of research in the biomedical field. In a not-so-distant past, the scientific community has witnessed the rise of immunotherapy based on immune checkpoint inhibitors (ICIs). This therapeutic modality intends to abolish immunosuppressive interactions, re-establishing T cell responses against metastasized cancer cells. Despite the initial enthusiasm, the ICIs were later found to be associated with low clinical therapeutic outcomes and immune-related side effects. To address these limitations, researchers are exploring the combination of ICIs with nanomaterial-mediated phototherapies. These nanomaterials can accumulate within the tumor and produce, upon interaction with light, a temperature increase (photothermal therapy) and/or reactive oxygen species (photodynamic therapy), causing damage to cancer cells. Importantly, these photothermal-photodynamic effects can pave the way for an enhanced ICI-based immunotherapy by inducing the release of tumor-associated antigens and danger-associated molecular patterns, as well as by relieving tumor hypoxia and triggering a pro-inflammatory response. This progress report analyses the potential of nanomaterial-mediated photothermal-photodynamic therapy in combination with ICIs, focusing on their ability to modulate T cell populations leading to an anti-metastatic abscopal effect and on their capacity to generate immune memory that prevents tumor recurrence.
- Environmentally-friendly reduced graphene oxide functionalized with hyaluronic acid for targeted cancer photothermal therapyPublication . Sousa, Ana Rita Lima; Diogo, Duarte de Melo; Alves, Cátia; Costa, Elisabete; Ferreira, Paula; Louro, Ricardo; Mendonça, António; Correia, I.J.Reduced Graphene Oxide (rGO) is one of the most promising nanomaterials for cancer photothermal therapy (PTT) due to its high near infrared (NIR) absorption. However, the rGO producing methods uses dangerous reducing agents, resulting in poor biocompatibility. Additionally, rGO also displays poor colloidal stability and is unable to target cancer cells. These limitations can be improved by using environmentally-friendly reduction methods and by functionalizing this nanomaterial with amphiphilic polymers. In this work, the production of reduced Graphene Oxide (rGO) rGO was performed by using an environmentally-friendly method (reduction with L-ascorbic Acid (LAA)). Then, the obtained rGO was functionalized with an amphiphilic polymer based on hyaluronic acid (HA-g-PMAO) for application in CD44-targeted breast cancer PTT
- Injectable in situ forming thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applicationsPublication . Sousa, Rita Lima; Diogo, Duarte de Melo; Alves, Cátia; Cabral, Cátia S. D.; Miguel, Sónia P.; Mendonça, António; Correia, I.J.Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.
- Poly(2-ethyl-2-oxazoline) functionalized reduced graphene oxide: Optimization of the reduction process using dopamine and application in cancer photothermal therapyPublication . Sousa, Ana Rita Lima; Alves, Cátia; Melo, Bruna L.; Moreira, André; Mendonça, António; Correia, I.J.; Diogo, Duarte de MeloThe high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 1:5 graphene oxide:dopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 ◦C (75 μg/mL; 808 nm, 1.7 W/cm2, 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability < 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy.