Desenvolvimento de nanomateriais para a terapia fototermal do cancro

Breast cancer is one of the most prevalent and one of the leading causes of cancer-related deaths among women worldwide. In the specific case of the Portuguese population, breast cancer incidence and mortality rates increased in the past years. This scenario is mostly owed to the ineffectiveness of the currently available treatments (surgery, radiotherapy and small molecule-based therapies), whose therapeutic success is hindered by safety issues, non-specific toxicity and resistance mechanisms displayed by cancer cells to drugs. Such emphasizes the demand for a plethora of novel therapeutic approaches. In the past decades, light-induced therapies have started to be investigated as alternative strategies to combat cancer. These treatment modalities comprise photodynamic therapy (PDT) and photothermal therapy (PTT). Both therapeutic approaches depend on the external irradiation of the tumor region with near-infrared (NIR) light for activating photosensitizers or photothermal agents, that lead to the generation of reactive oxygen species (ROS; in PDT) or to a temperature increase (in PTT), which have a cytotoxic effect on cancer cells. Yet, such treatments still need to be further improved in what concerns their efficacy and selectivity towards the tumor region. Recently, the entrapment of NIR photoabsorbers in nanoparticles surpassed problems like the poor solubility of these molecules in biological fluids. Moreover, nanoparticles due to their physicochemical properties can display a preferential tumor accumulation, which is crucial for increasing the loaded NIR photoabsorbers bioavailability and ultimately the efficacy and selectivity of this therapeutic approach. Herein, a novel nanovehicle loaded with a NIR dye aimed for breast cancer phototherapy was developed. To accomplish that, two vitamin E derivatives, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and D-α-tocopheryl succinate (TOS), were used to assemble amphiphilic micelles with a core-shell structure. TPGS and TOS were selected due to their intrinsic anticancer activity (e.g. through the generation of ROS) and ability to encapsulate poorly water-soluble molecules. 2-[2-[2-Chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) was chosen due to its versatile nature as a NIR light-responsive compound (photothermal agent, photosensitizer and NIR imaging dye). IR780-loaded TPGS-TOS micelles (IR780-TTM) with suitable sizes were obtained by using specific TPGS and TOS weight feed ratios during micelles formulation and these were able to encapsulate IR780 with high efficiency. In in vitro assays, the IR780-TTM induced a cytotoxic effect in cancer cells upon exposure to NIR irradiation through the generation of reactive oxygen species (PDT). This effective ablation of cancer cells was achieved using an ultra-low IR780 concentration. Moreover, IR780-TTM also demonstrated the ability to act as photothermal and imaging agents. Overall, the novel micellar nanoplatforms developed in this study possess a huge potential for breast cancer PDT. Moreover, IR780-TTM also demonstrate promising results to act as photothermal and imaging agents, which widens their applicability for the treatment and diagnosis of cancer.O cancro da mama é um dos mais prevalentes e uma das principais causas de morte das mulheres em todo o mundo. No caso específico da população Portuguesa, as taxas de incidência e mortalidade associadas ao cancro da mama têm vindo a aumentar nos últimos anos. Este cenário deve-se maioritariamente à ineficácia dos tratamentos atualmente disponíveis (cirurgia, radioterapia e terapias baseadas em pequenas moléculas), cuja eficácia terapêutica é reduzida devido a problemas de segurança, toxicidade não específica e ainda devido aos mecanismos de resistência a fármacos que as células cancerígenas apresentam. Estes factos evidenciam a necessidade de desenvolver novas abordagens terapêuticas. Nas últimas décadas, as fototerapias têm sido investigadas como estratégias alternativas para combater as células cancerígenas. Estas modalidades terapêuticas incluem a terapia fotodinâmica e a fototérmica. Ambos os tratamentos dependem da irradiação da região tumoral com radiação com um comprimento de onda próximo do infravermelho (near-infrared (NIR)) que ativa moléculas fotoresponsivas, as quais induzem a produção de espécies reativas de oxigénio (terapia fotodinâmica) ou um aumento de temperatura (terapia fototérmica), que têm um efeito citotóxico nas células cancerígenas. Porém, estes tratamentos ainda têm que ser otimizados para incrementar a sua eficácia e seletividade para o tumor. A nanotecnologia tem permitido ultrapassar algumas das principais limitações da aplicação das fototerapias no tratamento do cancro, através da encapsulação de agentes fotoresponsivos em nanopartículas. A encapsulação de moléculas fotoresponsivas à luz NIR em nanoveículos é crucial para reverter a baixa solubilidade destas moléculas em fluidos biológicos. Para além disso, estes nanotransportadores acumulam-se preferencialmente no tumor devido às suas propriedades físico-químicas, o que permite aumentar a biodisponibilidade das moléculas fotoresponsivas encapsuladas nestes, melhorando assim a eficácia e seletividade destas abordagens terapêuticas. Na presente tese é descrito o desenvolvimento de um nanoveículo com capacidade de encapsular um agente fotoresponsivo à luz NIR, para aplicação na fototerapia do cancro da mama. Para tal, foram utilizados dois derivados de vitamina E, succinato de D-α-tocoferil polietilenoglicol 1000 (TPGS) e succinato de D-α-tocoferil (TOS), para formular micelas anfifílicas com uma estrutura tipo “núcleo-concha”. O TPGS e o TOS foram selecionados por apresentarem atividade anticancerígena intrínseca (por exemplo, através da produção de espécies reativas de oxigénio) e pela sua capacidade para encapsular moléculas pouco solúveis em água. O iodeto de 2-[2-[2-cloro-3-[(1,3-dihidro-3,3-dimetil-1-propil-2H-indol-2-ilideno) etilideno]-1-ciclohexeno-1-il]etenil]-3,3-dimetil-1-propilindólio (IR780) foi escolhido devido à sua versatilidade como molécula fotoresponsiva, uma vez que possui características que permitem a sua aplicação como agente fototerapêutico (terapia fotodinâmica e fototermal) e de diagnóstico. No presente estudo foram obtidas micelas de TPGS-TOS contendo IR780 (IR780-TTM) com características físico-químicas adequadas, utilizando proporções de TPGS e TOS específicas aquando da sua formulação. As micelas produzidas permitiram a encapsulação do IR780 com elevada eficiência. Nos ensaios in vitro realizados verificou-se que as IR780-TTM medeiam um efeito citotóxico nas células cancerígenas após irradiação com luz NIR, através da produção de espécies reativas de oxigénio (terapia fotodinâmica). Esta eficiente ablação das células cancerígenas foi alcançada usando uma concentração de IR780 mais baixa do que a que foi descrita até agora na literatura. Aliado a isto, constatou-se que as IR780-TTM demonstram potencial para serem utilizadas como agentes de fototermia e imagiologia. Em suma, os nanoveículos desenvolvidos na presente tese apresentam um enorme potencial para a terapia fotodinâmica do cancro da mama. Por outro lado, as propriedades fototérmicas e imagiológicas que as IR780-TTM apresentam aumentam a aplicabilidade destas micelas no tratamento e diagnóstico do cancro

How do we live with chronic disease?: a rights-based approach promoting the wellbeing of children with chronic disease

This paper focuses on the life experiences of children with chronic disease, a group whose invisibility involves particular challenges in their relationship with professionals in important life contexts, such as family, school and hospital. The study includes two complementary phases: i) Phase 1, composed of 15 interviews with parents, education and health professionals and two focus group discussions with children, and children and their mothers; and ii) Phase 2, which included self-report questionnaires administered to parents (n = 152) and children with chronic disease (n = 176). Based on a mixed methodology, this study combines quantitative and qualitative methods assuming that plural approaches allow for a deeper understanding of the life conditions of children with chronic disease and their families. The results reinforce the reproduction of social stereotypes and the tendency to focus on the individual ability to solve problems, which still remain to be circumscribed to the people's chronic disease sphere. Moreover, this paper reveals the central role that inclusive contexts have on children's wellbeing

A case study with PMatE in the learning of mathematical subjects at university level

Since 1989, the Mathematics Education Project (PmatE – Projecto Matemática Ensino) has developed several strategies to increase the interest and improve the success of students in Mathematics. PmatE developed a platform of computer aided education (PCA), currently available only in the internet, including all grades since primary school. The main goal of this platform is to support teaching, being a tool that allows: the management of the groups involved; the elaboration of tests; the research of student performance; the analysis of results and other functionalities of management. The developed programs are a tool to support education, evaluation and learning. It’s presented a case study with Science Food Engineering students. The major goal of the study is to evaluate the impact of the platform of computer aided education (PCA) developed for the PmatE in the learning of mathematical subjects at the University level. This paper describes how it is conceived as well as the main results

Interlacing mathematics and art: hands-on non-Euclidean geometry

Elliot Eisner (1933-2014), a pioneer in arts education, suggested that an artistic approach to education could improve its quality and lead to a new vision for teaching and learning. This is true for any subject, including mathematics. Geometry related topics make a perfect setting for a deeper contribution of art to education. One such topic is the study of non-Euclidean geometry. In this paper, we present some results of a professional development course for mathematics teachers where the participants studied non-Euclidean geometry concepts. The participants created ceramic pieces using the Poincaré disk and styrofoam balls covered with fabrics using spherical geometry.publishe

Does PmatE help students to be more autonomous in the learning of mathematical subjects at university level?

Since 1989, the Mathematics Education Project (PmatE – Projecto Matemática Ensino) has developed several strategies to increase the interest and improve the success of students in Mathematics. PmatE developed a platform of computer aided education (PCA), currently available only in the internet, including all grades since primary school. The main goal of this platform is to support teaching, being a tool that allows: the management of the groups involved; the elaboration of tests; the research of student performance; the analysis of results and other functionalities of management. The developed programs are a tool to support education, evaluation and learning. However, this platform has not yet been subject to a systematic evaluation, especially at the superior education level, that will allow us to conclude whether its goals have been achieved. From this standpoint, we develop a case study with Science Food Engineering students. In this article, we discuss the resonance of the platform of computer aided education (PCA) developed for the PmatE in terms of the autonomy skills development. This paper describes how it is conceived as well as the main results. We concluded that, although recognized the platform potential, a considerable number of students preferred a more traditional approach

A plataforma PmatE e o desenvolvimento de apetências em Matemática

A era da informação e o desenvolvimento das tecnologias de informação e comunicação vêm colocar novos desafios e oportunidades às instituições de Ensino Superior, nomeadamente, ao nível do processo educativo, que deve ser mais centrado no aluno e nas suas aprendizagens. Assim, desenvolveu-se um estudo de caso, envolvendo alunos do curso de Engenharia Alimentar, que perseguiu como principal objetivo avaliar o impacto da exploração diferenciada da plataforma de ensino assistido, desenvolvida pelo Projeto Matemática Ensino (PmatE), como complemento à abordagem didática da unidade temática “Cálculo Integral em IR”. Neste artigo, discute-se a sua ressonância ao nível do desenvolvimento de apetências relativamente à matemática, manifestadas através dum maior interesse por parte dos alunos em relação à unidade curricular e concluiu-se que o uso da plataforma contribuiu para aumentar o gosto pela Matemática.The information age and the development of information and communication technologies brings new challenges and opportunities for higher education institutions, namely, in the educational process, which should be more focused in the student and in his learning process. Thus, a case study was developed with Science Food Engineering students. The major goal of the study is to evaluate the impact of a differential use of the platform developed for the PmatE in the process of learning math subjects at the University level. In this article, we discuss the resonance of the platform of computer aided education (PCA) developed for the PmatE in terms of mathematics appetencies, manifested through a larger interest of the students in relation to the curricular unit. We can conclude that the use of PmatE platform contributed to increase the liking for mathematics.La era de la información y el desarrollo de las nuevas tecnologías de información y comunicación colocan nuevas cuestiones y exigen un reposicionamiento de las instituciones de Enseñanza Superior, que enfrentan nuevos retos y oportunidades, nombradamente, en el proceso de enseñanza y de aprendizaje, que debe ser más centrado en el alumno y en sus aprendizajes. Por eso, se desarrolló un estudio de caso, involucrando estudiantes de la carrera de Ingeniaría Alimentar, que tuvo como principal objetivo evaluar el impacto de la exploración diferenciada de la plataforma de enseñanza asistida desarrollada por el Proyecto Matemática Enseñanza (PmatE), como complemento al abordaje didáctico de la unidad temática “Cálculo Integral en IR”. En este artículo, se discute su resonancia a nivel del desarrollo de antojos relativamente a la matemática, manifestadas a través de un mayor interés por parte de los estudiantes en relación a la unidad curricular y se concluyó que, el uso de la plataforma contribuyó para el aumentar del gusto por la Matemática

The use of mathematics education project in the learning of mathematical subjects at university level

The educational context requires a renewal of paradigms. Profound changes in the roles and functions of teachers and students are particularly vital. More active, cooperative and participative methodologies of learning must be privileged, breaking with magisterial education and the mere ‘transmission’ of knowledge. Informatics tools can become a major element in the educational context, promoting significant and self-regulated learning for the student, always under the adequate orientation of the teacher. In this context, the Mathematics Education Project (PmatE) was created in the University of Aveiro, with the main objective of identifying and counteracting the causes of school failure in mathematics in an innovative approach. However, the PmatE platform has not yet been subjected to the kind of systematic evaluation, especially in higher education, that would allow us to understand in what conditions the goals can be achieved. Thus, the question underlying this explanatory research is: “What impact does the platform of assisted education developed by PmatE have in the process of learning math subjects at university level?” A previous analysis (still ongoing) of the data collected through several techniques – inquiry, documental analysis and participant observation – suggests there are interesting and innovative alternatives to the dominant pedagogies in higher education (where teaching assumes almost exclusively a magisterial form), with significant advantages for the construction of knowledge and for the development of the students’ capabilities

Recursos pessoais e contextuais preditores de perceção de saúde na adolescência

Self-Rated Health is the product of the interaction between personal characteristics and contextual conditions. It reflects the resources of the person, and it consists in a dynamic evaluation, i.e., a personal judgment that reflects both a point-in-time status and a developmental process. The Developmental Assets® framework provides a holistic approach in to the understanding of development, which focuses on resources that can be explored both at individual and contextual levels, in order to foster a healthy development. The purpose of this research is to explore the relationship between adolescents’ Perception of Health and their experience of Developmental Assets. A convenience sample of 503 Portuguese students was evaluated, mean age of 16 years (SD = 1.2), 63% of female gender. Results indicate that better Health Perception is associated with greater experience of Developmental Assets. Results suggest the impact of a subset of Developmental Assets on Health prediction, with Internal Assets being the strongest predictors. Results suggest the theoretical and practical utility of the Developmental Assets® framework for the understanding of Health Perception in adolescents.La Percepción de Salud es el producto de la interacción entre características personales y condiciones contextuales. Esto refleja los recursos de la persona, así como consiste en una evaluación dinámica, un juicio que refleja el estado y el proceso de desarrollo. El Modelo de Recursos del Desarrollo - Developmental Assets® - proporciona un enfoque holístico en la comprensión del desarrollo, foco en Recursos que pueden ser explorados tanto a nivel individual, como contextual para propiciar a los adolescentes un desarrollo saludable. El objetivo del presente estudio consiste en explorar la relación entre la Percepción de Salud y la experiencia de Recursos del Desarrollo. Se evaluó una muestra de conveniencia constituida por 503 estudiantes portugueses, con edades comprendidas entre los 13 y 19 años (M = 16, DE = 1.2), mayoritariamente del género femenino (63%). Los resultados indican que la mejor percepción de la salud está asociada a la mayor experiencia de recursos del desarrollo. Los datos sugieren el impacto de un subconjunto de Recursos en la predicción de Salud, constituyendo los Recursos Internos los predictores más fuertes. Se sugiere la utilidad teórica y práctica de la utilización del Modelo de Recursos del Desarrollo para la comprensión de la Percepción de Salud en adolescentes.A Perceção de Saúde é o produto da interação entre características pessoais e condições contextuais. Esta reflete os recursos da pessoa, assim como consiste numa avaliação dinâmica, um julgamento que reflete estado e processo de desenvolvimento. O Modelo de Recursos do Desenvolvimento – Developmental Assets® – proporciona uma abordagem holística na compreensão do desenvolvimento, foco em Recursos que podem ser explorados quer ao nível individual, quer contextual de modo a propiciar aos adolescentes um desenvolvimento saudável. O objetivo do presente estudo consiste em explorar a relação entre a Perceção de Saúde e a experiência de Recursos do Desenvolvimento. Foi avaliada uma amostra de conveniência constituída por 503 estudantes portugueses, com idades compreendidas entre os 13 e 19 anos (M = 16; DP = 1,2), maioritariamente do género feminino (63%). Os resultados indicam que melhor Perceção de Saúde está associada a maior experiência de Recursos do Desenvolvimento. Os dados sugerem o impacto de um subconjunto de Recursos na predição de Saúde, constituindo os Recursos Internos os preditores mais fortes. Sugere-se a utilidade teórica e prática da utilização do Modelo de Recursos do Desenvolvimento para a compreensão da Perceção de Saúde em adolescentes