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Projeto de investigação
Therapeutic deep eutectic systems as promising selective therapeutic agents in the anticancer battle
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Molecular landscape of therapeutic deep eutectic systems selective toxicity towards colorectal cancer
Publication . Oliveira, Filipe; Pinto, Joana; Amaro, Filipa; Pereira, Joana; Ferreira, Inês; Diniz, Mário S.; Pinho, Paula Guedes de; Duarte, Ana Rita C.; DQ - Departamento de Química; LAQV@REQUIMTE; UCIBIO - Applied Molecular Biosciences Unit; Elsevier BV
The foremost modern medicine challenges, such as cancer's high mortality rates, have emphasized the growing need for improved therapeutic agents. Following eutectic systems spotlight due to their remarkable physicochemical and biological properties, while mostly in compliance with the Green Chemistry Principles and sustainability metrics as the Sustainable Development Goals (SDG) from United Nations, we aimed to push forward their understanding as anticancer agents. Considering therapeutic deep eutectic systems (THEDES) promising reports of anticancer activity towards colorectal cancer (CRC) cells, we sought to fill the knowledge gap on these eutectics impact on these cancer cells molecular landscape. For that, an integrated approach was used to study how combining a terpene – as menthol (Me), thymol (Thy), perillyl alcohol (POH) and limonene (Lim) – with ibuprofen (Ibu) as a THEDES, affects permeability, cellular transport, cell viability, reactive oxygen species (ROS), cell metabolome and systemic toxicity. THEDES exposure resulted in increased Ibu cellular uptake, depletion of ROS, and cell dead induction via apoptosis. Moreover, CRC cells experienced alterations in their metabolite landscape with deleterious effects on essential metabolic pathways, such as lipid and anaerobic glycolysis energy production pathways. Furthermore, non-relevant systemic toxicity of these THEDES, within the range of concentrations tested, was observed. These findings underscore THEDES potential as selective anticancer agents, while offering a promising path for the development of therapeutics aligned with the sustainability metrics.
Alginate–Chitosan Membranes for the Encapsulation of Lavender Essential Oil and Development of Biomedical Applications Related to Wound Healing
Publication . Cruz Sánchez, Encarnación; García, María Teresa; Pereira, Joana; Oliveira, Filipe; Craveiro, Rita; Paiva, Alexandre; Gracia, Ignacio; García-Vargas, Jesús Manuel; Duarte, Ana Rita C.; LAQV@REQUIMTE; DQ - Departamento de Química; MDPI - Multidisciplinary Digital Publishing Institute
Biopolymers such as chitosan (CHT) or alginate (ALG) are among the most prominent for health-related applications due to their broad bioactivity. Their combination for the preparation of membranes is hereby proposed as an application for wound healing with the incorporation of lavender essential oil (LEO), widely known for its antioxidant and antimicrobial properties. The preparation of CHT, CHT + LEO, ALG, ALG + LEO, and CHT/ALG + LEO membranes was accomplished, and its composition was analyzed using Fourier Transform Infrared Spectroscopy (FTIR). The water absorption capacity and oil release profile of the membranes revealed higher water uptake capacity when a lower LEO release was obtained. The combined CHT/ALG + LEO film showed a water uptake percentage of 638% after 48 h and a maximum LEO release concentration of 42 mg/L. Cytotoxicity and biocompatibility of the prepared membranes were studied using a HaCaT cell line, with an assessment of cell viability regarding film leachables, DNA quantification, and DAPI-phalloidin staining. The results revealed that the indirect contact of the prepared membranes via its leachables does not compromise cell viability, and upon direct contact, cells do not adhere or proliferate on the surface of the membranes. Moreover, the CHT/ALG + LEO membrane increases cell proliferation, making it suitable for applications in wound healing.
Therapeutic deep eutectic systems towards the treatment of tuberculosis and colorectal cancer
Publication . Oliveira, Filipe; Santos, Filipa; Duarte, Ana Rita C.; DQ - Departamento de Química; LAQV@REQUIMTE; MDPI - Multidisciplinary Digital Publishing Institute
What if a new technology based on therapeutic deep eutectic systems would disrupt the current treatment of major economic and socially burdensome diseases? The classical definition of eutectic systems is that they are the combination of two or more compounds that interact via hydrogen bonds, from which results a melting temperature depression in comparison with that of its individual components. Therapeutic deep eutectic systems are defined as eutectic systems in which at least one of the individual components is an active pharmaceutical ingredient, or a eutectic system in which the active pharmaceutical ingredient is dissolved. Current literature reports on tuberculosis have been mostly based on the most common anti-tuberculosis drugs prescribed. Using eutectic systems based on naturally occurring molecules known for their anti-microbial activity may also present a promising therapeutic strategy able to cope with the prevalence of Mycobacterium tuberculosis and prevent the appearance of multidrug resistance strains. With regards to colorectal cancer, literature has been unravelling combinations of terpenes with anti-inflammatory drugs that are selectively cytotoxic towards colorectal cancer cells and do not compromise the viability of normal intestinal cells. This technology could contribute to preventing tumor growth and metastasis while providing a patient compliance therapeutics, which will be crucial to the success of overcoming the challenges presented by cancers.
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2021.07780.BD