Interfaces alternativas para brinquedos adaptados

O presente artigo descreve o trabalho desenvolvido durante o ano letivo 2015/2016 no âmbito da unidade curricular de Projeto em Engenharia Eletrotécnica e de Computadores do curso de Licenciatura em EngenhariaEletrotécnica e de Computadores da Escola Superior de Tecnologia e Gestão (ESTG). São apresentadasideias e objetivos, bem como as metodologias de trabalho utilizadas e os protótipos desenvolvidos deforma a tornar a interação de crianças com brinquedos adaptados mais simples e divertida. Em conjuntocom a campanha “Mil Brinquedos Mil Sorrisos” foram definidas algumas estratégias para melhorar esta interaçãoatravés da inovação e melhoramento dos dispositivos já desenvolvidos. Numa primeira abordagem foi efetuada uma pesquisa sobre as interfaces alternativas já existentes para brinquedosadaptados, sobre os requisitos necessários para cada sistema, o funcionamento e consumos energéticosde cada dispositivo e custos associados. Foram criados dois sistemas de interação: um com fios e outro sem fios, sendo este último constituído por dois elementos (interruptor emissor e recetor). Associado a este sistema sem fios, foi também desenvolvida uma aplicação para dispositivos móveis (sistema operativo Android) que permite ativar o brinquedo adaptado a partir de um Smartphone ou Tablet.info:eu-repo/semantics/publishedVersio

Avaliação da incorporação de levofloxacina em partículas de um biomaterial ortopédico para tratamento da osteomielite

Relatório de projecto no âmbito de Bolsa Universidade de Lisboa/Fundação Amadeu Dias (2010/2011). Universidade de Lisboa. Faculdade de FarmáciaA osteomielite consiste num processo inflamatório associado à destruição óssea, causado por microrganismos infecciosos. O seu tratamento envolve debridamento cirúrgico, remoção dos corpos estranhos e ainda antibioterapia. A necessidade de se atingirem concentrações parentéricas elevadas de antibióticos para que a terapêutica seja efectiva no tecido ósseo, assim como a duração prolongada do tratamento pode conduzir à toxicidade sistémica induzida pelo antibiótico. Este facto vem sublinhar a importância do desenvolvimento de sistemas de drug delivery, de forma a que a libertação dos fármacos no local pretendido, seja feita de modo controlado e por períodos de tempo mais longos. O poli(metilmetacrilato) (PMMA), tratando-se de um polímero biocompatível com valor reconhecido no âmbito das artroplastias, foi considerado como sistema de transporte para a libertação controlada de um antibiótico: a levofloxacina (LEV). O referido antibiótico é uma fluoroquinolona de 3ª geração geralmente utilizada contra Staphylococcus aureus, um dos agentes patogénicos frequentemente associados à osteomielite. Objectivos: 1) Incorporação de LEV em partículas de PMMA; 2) Comparação das características das partículas obtidas por diferentes métodos. Métodos: 1) As partículas de PMMA foram preparadas pelo método da dupla emulsão a/o/a com evaporação do solvente (DESE), quer pela via convencional quer por downscale. Foram avaliados diversos parâmetros como sejam a morfologia, o rendimento de produção, o tamanho, a eficiência de encapsulação (EE), o drug loading (DL), o potencial zeta (PZ) e o perfil de libertação in vitro. Resultados: 1) As partículas apresentaram superfície esférica e regular e tamanhos na gama do micrómetro (µm). Obtiveram-se melhores resultados quer de DL quer de EE, pelo método convencional. Os ensaios de libertação in vitro revelaram concentrações inferiores ao da MIC50 para S. aureus durante toda a duração do ensaio. 2) As partículas produzidas pelo método convencional destacaram-se especialmente das produzidas por downscale no que diz respeito aos seus tamanhos e à dispersão da população. Conclusões: Os valores alcançados revelaram que tanto para o método convencional como para o de downscale é necessário levar a cabo algumas alterações na formulação de forma a melhorar a encapsulação da LEV, a distribuição do tamanho das partículas (essencialmente a nível do downscale) e também os perfis de libertação in vitro

Nanomedicine-based strategies to target and modulate the tumor microenvironment

Funding Information: The authors acknowledge financial support from Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). Funding Information: The authors acknowledge financial support from Funda??o para a Ci?ncia e a Tecnologia/ Minist?rio da Ci?ncia, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). None declared by authors. Publisher Copyright: © 2021 Elsevier Inc.The interest in nanomedicine for cancer theranostics has grown significantly over the past few decades. However, these nanomedicines need to overcome several physiological barriers intrinsic to the tumor microenvironment (TME) before reaching their target. Intrinsic tumor genetic/phenotypic variations, along with intratumor heterogeneity, provide different cues to each cancer type, making each patient with cancer unique. This brings additional challenges in translating nanotechnology-based systems into clinically reliable therapies. To develop efficient therapeutic strategies, it is important to understand the dynamic interactions between TME players and the complex mechanisms involved, because they constitute invaluable targets to dismantle tumor progression. In this review, we discuss the latest nanotechnology-based strategies for cancer diagnosis and therapy as well as the potential targets for the design of future anticancer nanomedicines.publishersversionpublishe

Machine learning for next-generation nanotechnology in healthcare

Funding: The authors acknowledge financial support from FCT Portugal in the framework of PhD grant 2020.06638.BD (to D.P.S.), and the European Research Council grant agreement 848325 (J. Conde for the ERC Starting Grant). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/ 00684/2018).Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pipelines.publishersversionpublishe

from Machine Learning Screening to In Vivo Efficacy

© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.Despite improvements in cancer survival rates, metastatic and surgery-resistant cancers, such as pancreatic cancer, remain challenging, with poor prognoses and limited treatment options. Enhancing drug bioavailability in tumors, while minimizing off-target effects, is crucial. Metal-organic frameworks (MOFs) have emerged as promising drug delivery vehicles owing to their high loading capacity, biocompatibility, and functional tunability. However, the vast chemical diversity of MOFs complicates the rational design of biocompatible materials. This study employed machine learning and molecular simulations to identify MOFs suitable for encapsulating gemcitabine, paclitaxel, and SN-38, and identified PCN-222 as an optimal candidate. Following drug loading, MOF formulations are improved for colloidal stability and biocompatibility. In vitro studies on pancreatic cancer cell lines have shown high biocompatibility, cellular internalization, and delayed drug release. Long-term stability tests demonstrated a consistent performance over 12 months. In vivo studies in pancreatic tumor-bearing mice revealed that paclitaxel-loaded PCN-222, particularly with a hydrogel for local administration, significantly reduced metastatic spread and tumor growth compared to the free drug. These findings underscore the potential of PCN-222 as an effective drug delivery system for the treatment of hard-to-treat cancers.publishersversionepub_ahead_of_prin

Biopolymeric Coatings for Local Release of Therapeutics from Biomedical Implants

Funding Information: S.T., B.M., and J.C. contributed equally to this work. The authors are grateful for funding received from the Australian Research Council Centre of Excellence program (Project Number CE 140100012). J.C. acknowledges the European Research Council Starting Grant (ERC‐StG‐2019‐848325). S.N. and F.D. acknowledge the financial support of Australian Research Council through DP200102164. Publisher Copyright: © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here advances in delivery of drugs from bone, brain, ocular, and cardiovascular implants are reviewed. These areas are focused to highlight that both hard and soft tissue implants can benefit from controlled localized delivery. The composition of biopolymers used to achieve appropriate delivery to the selected tissue types, and their corresponding outcomes are brought to the fore. To conclude, key factors in designing drug-loaded biopolymeric coatings for biomedical implants are highlighted.publishersversionepub_ahead_of_prin

Nanodelivery of nucleic acids

Funding: This work was supported by the European Research Council (ERC) Starting Grant (ERC-StG-2019-848325 to J. Conde) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J. Conde). J.S. acknowledges US National Institute of Health (NIH) grants (R01CA200900, R01HL156362 and R01HL159012), the US DoD PRCRP Idea Award with Special Focus (W81XWH1910482), the Lung Cancer Discovery Award from the American Lung Association and the Innovation Discovery Grants award from the Mass General Brigham. H.L., D.Y. and X.Z. were supported by the National Key R&D Program of China (no. 2020YFA0710700), the National Natural Science Foundation of China (nos 21991132, 52003264, 52021002 and 52033010) and the Fundamental Research Funds for the Central Universities (no. WK2060000027).There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting. Nucleic acid therapeutics such as antisense DNA, mRNA, small interfering RNA (siRNA) or microRNA (miRNA) have been widely explored to modulate DNA or RNA expression Strikingly, gene therapies combined with nanoscale delivery systems have broadened the therapeutic and biomedical applications of these molecules, such as bioanalysis, gene silencing, protein replacement and vaccines. Here, we overview how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. It is crucial to outline some of the general design considerations of nucleic acid delivery nanoparticles, their extraordinary properties and the structure–function relationships of these nanomaterials with biological systems and diseased cells and tissues.publishersversionpublishe

A Fluorinated BODIPY-Based Zirconium Metal-Organic Framework for In Vivo Enhanced Photodynamic Therapy

Photodynamic therapy (PDT), an emergent noninvasive cancer treatment, is largely dependent on the presence of efficient photosensitizers (PSs) and a sufficient oxygen supply. However, the therapeutic efficacy of PSs is greatly compromised by poor solubility, aggregation tendency, and oxygen depletion within solid tumors during PDT in hypoxic microenvironments. Despite the potential of PS-based metal-organic frameworks (MOFs), addressing hypoxia remains challenging. Boron dipyrromethene (BODIPY) chromophores, with excellent photostability, have exhibited great potential in PDT and bioimaging. However, their practical application suffers from limited chemical stability under harsh MOF synthesis conditions. Herein, we report the synthesis of the first example of a Zr-based MOF, namely, 69-L2, exclusively constructed from the BODIPY-derived ligands via a single-crystal to single-crystal post-synthetic exchange, where a direct solvothermal method is not applicable. To increase the PDT performance in hypoxia, we modify 69-L2 with fluorinated phosphate-functionalized methoxy poly(ethylene glycol). The resulting 69-L2@F is an oxygen carrier, enabling tumor oxygenation and simultaneously acting as a PS for reactive oxygen species (ROS) generation under LED irradiation. We demonstrate that 69-L2@F has an enhanced PDT effect in triple-negative breast cancer MDA-MB-231 cells under both normoxia and hypoxia. Following positive results, we evaluated the in vivo activity of 69-L2@F with a hydrogel, enabling local therapy in a triple-negative breast cancer mice model and achieving exceptional antitumor efficacy in only 2 days. We envision BODIPY-based Zr-MOFs to provide a solution for hypoxia relief and maximize efficacy during in vivo PDT, offering new insights into the design of promising MOF-based PSs for hypoxic tumors

A Fluorinated BODIPY-Based Zirconium Metal-Organic Framework for In Vivo Enhanced Photodynamic Therapy

Funding Information: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (NanoMOFdeli), ERC-2016-COG 726380, and the EPSRC (EP/S009000/1). This work was supported by the FCT PhD Scholarship (2020.06638.BD, Diana P. Sousa) and the European Research Council Starting Grant ERC-StG-2019-848325 (2019–2024, João Conde, João Conniot, and Bárbara Mendes). The Talos F200X G2 TEM was supported through an EPSRC Underpinning Multi-User Equipment Grant (EP/P030467/1). The authors thank the staff of PROXIMA-2A (Soleil Synchrotron, France) for assistance and acknowledge the beamtime under the in-house research proposal 99220022 and standard proposal 20220874. They also thank Dr. Karin Mueller and Dr. Filomena Gallo from the Cambridge Advanced Imaging Centre, Department of Physiology and Neuroscience, University of Cambridge, for assistance in performing TEM imaging on the stained cells. The authors thank Histopathology Unit at Gulbenkian Science Institute for quantitative pathology evaluation and Histological Facility at Nova Medical School for technical assistance in sample preparation. TOC and a,b were created with BioRender.com. Publisher Copyright: © 2024 The Authors. Published by American Chemical SocietyPhotodynamic therapy (PDT), an emergent noninvasive cancer treatment, is largely dependent on the presence of efficient photosensitizers (PSs) and a sufficient oxygen supply. However, the therapeutic efficacy of PSs is greatly compromised by poor solubility, aggregation tendency, and oxygen depletion within solid tumors during PDT in hypoxic microenvironments. Despite the potential of PS-based metal-organic frameworks (MOFs), addressing hypoxia remains challenging. Boron dipyrromethene (BODIPY) chromophores, with excellent photostability, have exhibited great potential in PDT and bioimaging. However, their practical application suffers from limited chemical stability under harsh MOF synthesis conditions. Herein, we report the synthesis of the first example of a Zr-based MOF, namely, 69-L2, exclusively constructed from the BODIPY-derived ligands via a single-crystal to single-crystal post-synthetic exchange, where a direct solvothermal method is not applicable. To increase the PDT performance in hypoxia, we modify 69-L2 with fluorinated phosphate-functionalized methoxy poly(ethylene glycol). The resulting 69-L2@F is an oxygen carrier, enabling tumor oxygenation and simultaneously acting as a PS for reactive oxygen species (ROS) generation under LED irradiation. We demonstrate that 69-L2@F has an enhanced PDT effect in triple-negative breast cancer MDA-MB-231 cells under both normoxia and hypoxia. Following positive results, we evaluated the in vivo activity of 69-L2@F with a hydrogel, enabling local therapy in a triple-negative breast cancer mice model and achieving exceptional antitumor efficacy in only 2 days. We envision BODIPY-based Zr-MOFs to provide a solution for hypoxia relief and maximize efficacy during in vivo PDT, offering new insights into the design of promising MOF-based PSs for hypoxic tumors.publishersversionpublishe

Multiscale Profiling of Nanoscale Metal-Organic Framework Biocompatibility and Immune Interactions

Funding Information: D.F.\u2010J. thanks the Royal Society for funding through University Research Fellowships and the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (NanoMOFdeli), ERC\u20102016\u2010COG 726380. The authors thank the EPSRC (grant EP/S009000/1). D.M. acknowledges NanoDTC Cambridge \u2013 EPSRC EP/S022953/1. X.L. acknowledges funding from Asthma + Lung UK (previously the British Lung Foundation). The authors are thankful for the technical support from the Cellular Imaging and Analysis Facility at the Department of Veterinary Medicine, University of Cambridge. The authors acknowledge the Laborat\u00F3rio de An\u00E1lises/REQUIMTE/LAQV for the acquisition of the ICP\u2010OES data. Publisher Copyright: © 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.The clinical translation of metal-organic frameworks (MOFs) – a promising class of porous materials for nanomedicine – is hindered by a poor understanding of their complex interactions with the immune system and in vivo immunotoxicity. To address this gap, a hierarchical “Safety-by-Design” pipeline is established and validated, integrating machine learning (ML) with ex vivo human blood studies and targeted in vivo models. This multi-stage workflow enables the systematic profiling of MOF immunotoxicity, de-risking their development. The power of this approach is demonstrated using four clinically relevant MOFs – NU-901, PCN-222, UiO-66, and ZIF-8 – revealing distinct, framework-dependent immune fingerprints. The initial in silico screening correctly flagged NU-901 and ZIF-8 as potential hazards to human health. These predictions are subsequently validated ex vivo, where NU-901 is confirmed to be selectively cytotoxic to CD14+ monocytes, and ZIF-8 is identified as a specific pro-inflammatory agent via IL-6 induction. In contrast, candidates predicted to be safe – UiO-66 and PCN-222 – demonstrated high biocompatibility ex vivo and advanced to in vivo studies, where they caused only minimal and transient immune activation. This study provides a validated, resource-efficient roadmap for preclinical immunotoxicity assessment, establishing a rational paradigm to accelerate the safe clinical translation of MOFs and other advanced nanomedicines.publishersversioninpres