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

Hydrogels for RNA delivery

Funding Information: This work was supported by the US National Institutes of Health grants R01CA200900, R01HL156362, R01HL159012 and R01HL162367 (to J.S.), the Lung Cancer Discovery Award from the American Lung Association (to J.S.), the Innovation Discovery Grants award from the Mass General Brigham (to J.S.), the European Research Council Starting Grant (ERC-StG-2019-848325 to J.C. and B.B.M.) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J.C.). Publisher Copyright: © 2023, Springer Nature Limited.RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy. Specifically, hydrogels can be engineered to exert precise spatiotemporal control over the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This Review provides a comprehensive overview of hydrogel loading of RNAs and hydrogel design for controlled release, highlights their biomedical applications and offers our perspectives on the opportunities and challenges in this exciting field of RNA delivery.publishersversionepub_ahead_of_prin

Natural materials

The use of naturally occurring materials as scaffolds to support cell growth and proliferation significantly impacted the origin and progress of tissue engineering and regenerative medicine. However, the majority of these materials failed to provide adequate cues to guide cell differentiation toward the formation of new tissues. Over the past decade, a new generation of multifunctional and smart natural-based materials has been developed to provide biophysical and biochemical cues intended to specifically guide cell behavior. In this chapter, the use of extracellular matrix proteins and blood-derivatives intrinsic capacity to mimic the biophysical and biological characteristics of native tissues is reviewed. Furthermore, the design of a variety of nanostructures using the well-explored characteristics of nucleic acids is summarized. In the second section, the exploitation of supramolecular chemistry to create new dynamic functional hydrogels that mimic the extracellular matrix structure and/or composition is surveyed. Then, the incorporation of nanoelements in polymeric networks for the design of smart nanocomposite materials with tailored functionalities to guide cell behavior is introduced. Finally, the future perspectives in the development of new biomaterials for tissue engineering and regenerative medicine are presented.Te authors acknowledge the fnancial support of the European Union Framework Programme for Research and Innovation Horizon 2020, under the TEAMING grant agreement No 739572 – Te Discoveries CTR, Marie Skłodowska-Curie grant agreement No 706996 and European Research Council grant agreement No 726178; FCT (Fundação para a Ciência e a Tecnologia) and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of Ph.D. grants PD/BD/113807/2015 (BBM) and PD/BD/129403/2017 (SMB), Post-Doc grant SFRH/ BPD/112459/2015 (RMD) and project SmarTendon (PTDC/NAN-MAT/30595/2017); Project NORTE01-0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF

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

Human-based nanocomposite cryogels for hemostatic and wound healing applications

In trauma surgery, a fast and effective hemostatic agent is crucial to prevent death. The current used hemostatic sponges are highly effective in stopping the hemorrhages, however they have a limited stability, shape memory, and biological functionality to induce an efficient regenerative healing after injury. Blood derivatives have attracted great attention as an inexpensive milieu of bioactive molecules (e.g., growth factors, cytokines), self-assembling scaffolding proteins (e.g., fibrinogen, fibronectin, vitronectin), and antimicrobial peptides (e.g., platelet factor-4) that have the ability to enhance angiogenesis, stem cell recruitment, and tissue regeneration. Among those, platelet lysate (PL) has attracted great attention as a milieu of supra-physiological doses of biomolecules that can be easily standardized. However, the current PL scaffolds showed limited stability and weak mechanical strength, which severely limits its performance as a bioinstructive and hemostatic biomaterial. Herein, we propose the use of aldehyde-functionalized CNC (a-CNC) that will be crosslinked through reversible Schiff base bonds established with the amine groups of PL proteins to produce a stable hemostatic cryogel for wound healing applications.EU’s H2020 programme for grant agreement 706996 and 739572 - The Discoveries CTR; FCT for SFRH/BPD/112459/2015, PD/BD/113807/2015, FOOD4CELLS (PTDC/CTM-BIO/4706/2014-POCI-01- 0145- FEDER 016716) and project NORTE-01-0145- FEDER-000021

Injectable and magnetic responsive hydrogels with bioinspired ordered structures

Injectable hydrogels are particularly interesting for applications in minimally invasive tissue engineering and regenerative medicine strategies. However, the typical isotropic microstructure of these biomaterials limits their potential for the regeneration of ordered tissues. In the present work, we decorated rod-shaped cellulose nanocrystals with magnetic nanoparticles and coated these with polydopamine and polyethylene glycol polymer brushes to obtain chemical and colloidal stable nanoparticles. Then, these nanoparticles (0.1-0.5 wt %) were incorporated within gelatin hydrogels, creating injectable and magnetically responsive materials with potential for various biomedical applications. Nanoparticle alignment within the hydrogel matrix was achieved under exposure to uniform low magnetic fields (108 mT), resulting in biomaterials with directional microstructure and anisotropic mechanical properties. The biological performance of these nanocomposite hydrogels was studied using adipose tissue derived human stem cells. Cells encapsulated in the nanocomposite hydrogels showed high rates of viability demonstrating that the nanocomposite biomaterials are not cytotoxic. Remarkably, the microstructural patterns stemming from nanoparticle alignment induced the directional growth of seeded and, to a lower extent, encapsulated cells in the hydrogels, suggesting that this injectable system might find application in both cellular and acellular strategies targeting the regeneration of anisotropic tissues.Fundação para a Ciência e a Tecnologia for SFRH/BPD/112459/2015 (RD), EU’s H2020 programme for Marie Skłodowska-Curie grant agreement 706996 and for European Research Council grant agreement 772817 - MagTendon, project RECOGNIZE (UTAPICDT/CTM-BIO/0023/2014), project FOOD4CELLS (PTDC/CTM-BIO/4706/2014 - POCI-01- 0145-FEDER 016716) (PB), and project NORTE-01-0145-FEDER-000021

Determinação experimental da função de aceitação angular de concentradores V-trough e CPC

Para analizar la cantidad de energía que un concentrador puede captar, es necesario que sean conocidas sus propiedades ópticas, siendo la función de aceptación angular una de las principales, porque permite, entre otras posibilidades, que sean determinados los limites operacionales de incidencia de los rayos. Este trabajo presenta los resultados experimentales de la aplicación de una metodología para la obtención de la función de aceptación angular. Para ello, fueran utilizados dos concentradores, un V-trough y un CPC, que fueron desarrollados para este experimento. Para el concentrador V-trough, los resultados obtenidos son próximos a los teóricos, con error promedio de 10%. Para el CPC, la función obtenida presenta valores menores que los teóricos, del orden de 50%, debido a las imperfecciones de la superficie, aunque el ángulo de corte obtenido sea mayor que el teórico, conforme a lo previsto en la literatura.Analyzing the amount of energy that a concentrator can capture, it´s necessary knowing its optical properties, the angular acceptance function is one of the main, because allows, beyond other possibilities, to determine the ray´s incidence operational limits. This work shows the experimental results obtained from a methodology to determine the angular acceptance function. It was used two solar concentrators: a V-trough and a CPC, that were developed for this experiment. The results obtained to the V-trough are near the theoretical, with a mean error of 10%. The function gotten to the CPC shows values lower than the theoretical off 50%, due to the surface imperfections, therefore the cut angle is larger than the theoretical, as foreseen in the literature.Tema 8: Energías renovables, modelización y simulación.Facultad de Arquitectura y Urbanism

Determinação experimental da função de aceitação angular de concentradores V-trough e CPC

Para analizar la cantidad de energía que un concentrador puede captar, es necesario que sean conocidas sus propiedades ópticas, siendo la función de aceptación angular una de las principales, porque permite, entre otras posibilidades, que sean determinados los limites operacionales de incidencia de los rayos. Este trabajo presenta los resultados experimentales de la aplicación de una metodología para la obtención de la función de aceptación angular. Para ello, fueran utilizados dos concentradores, un V-trough y un CPC, que fueron desarrollados para este experimento. Para el concentrador V-trough, los resultados obtenidos son próximos a los teóricos, con error promedio de 10%. Para el CPC, la función obtenida presenta valores menores que los teóricos, del orden de 50%, debido a las imperfecciones de la superficie, aunque el ángulo de corte obtenido sea mayor que el teórico, conforme a lo previsto en la literatura.Analyzing the amount of energy that a concentrator can capture, it´s necessary knowing its optical properties, the angular acceptance function is one of the main, because allows, beyond other possibilities, to determine the ray´s incidence operational limits. This work shows the experimental results obtained from a methodology to determine the angular acceptance function. It was used two solar concentrators: a V-trough and a CPC, that were developed for this experiment. The results obtained to the V-trough are near the theoretical, with a mean error of 10%. The function gotten to the CPC shows values lower than the theoretical off 50%, due to the surface imperfections, therefore the cut angle is larger than the theoretical, as foreseen in the literature.Tema 8: Energías renovables, modelización y simulación.Facultad de Arquitectura y Urbanism

CIÊNCIA NAS LICENCIATURAS?

We investigate how pre-service teachers understand science and some practices due to it and if they relate their scientific knowledge to the teacher undergraduate degree itself in which they are enrolled. The results were produced from the qualitative analyze of generated data through interviews with pre-service teachers of different teacher undergraduate degrees. We assume the antidisciplinary approach of Applied Linguistics, considering as main theoretical framework some scientific literacy studies located in different disciplines or fields of knowledge. The knowledge of science shared by research collaborators is linked more directly to the natural sciences; human sciences are reduced to a few numbers of disciplines and language studies are disregarded. This research contributes to recontextualize the scientific literacy studies in Applied Linguistics