Infrared-Emitting Multimodal Nanostructures for Controlled In Vivo Magnetic Hyperthermia

E.X. and R.M. contributed equally to this work. Work partially supported by the Ministerio de Ciencia, Innovacion y Universidades (PID2019-106301RB-I00 and PID2019-105195RA-I00), by the Spanish Ministry of Economy and Competitiveness (MAT2017-85617-R, SEV-2016-0686), by the Comunidad de Madrid (RENIM-CM, B2017/BMD-3867, co-financed by the European Structural and Investment Fund; NANOMAGCOST-CM P2018/NMT-4321), by the European COST Actions CA17115 (MyWave) and CA17140 (Nano2Clinic), by the Spanish Scientific Network HiperNano (RED2018-102626-T) and by the European Commission Horizon 2020 project NanoTBTech (Grant Number: 801305). D.G.-C. acknowledges CAM for funding PEJ-2018-AI/IND-11245. A.B. acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. E.X. is grateful for a Juan de la Cierva Formacion scholarship (FJC2018-036734-I). R.M. acknowledges the support of the European Commission through the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant agreement N 797945 (LANTERNS). A. E. acknowledges the support from Comunidad de Madrid (Talento project 2018-T1/IND-1005) and from AECC (Ideas Semilla 2019 project). P.R.S. is grateful for a Juan de la Cierva Incorporacion scholarship (IJC2019-041915-I). Procedures involving animal experiments were approved by the regional authority for animal experimentation of the Comunidad de Madrid and were conducted in agreement with the Universidad Autonoma de Madrid Ethics Committee, in compliance with the European Union directives 63/2010UE and Spanish regulation RD 53/2013.Deliberate and local increase of the temperature within solid tumors represents an effective therapeutic approach. Thermal therapies embrace this concept leveraging the capability of some species to convert the absorbed energy into heat. To that end, magnetic hyperthermia (MHT) uses magnetic nanoparticles (MNPs) that can effectively dissipate the energy absorbed under alternating magnetic fields. However, MNPs fail to provide real-time thermal feedback with the risk of unwanted overheating and impeding on-the-fly adjustment of the therapeutic parameters. Localization of MNPs within a tissue in an accurate, rapid, and cost-effective way represents another challenge for increasing the efficacy of MHT. In this work, MNPs are combined with state-of-the-art infrared luminescent nanothermometers (LNTh; Ag2S nanoparticles) in a nanocapsule that simultaneously overcomes these limitations. The novel optomagnetic nanocapsule acts as multimodal contrast agents for different imaging techniques (magnetic resonance, photoacoustic and near-infrared fluorescence imaging, optical and X-ray computed tomography). Most crucially, these nanocapsules provide accurate (0.2 degrees C resolution) and real-time subcutaneous thermal feedback during in vivo MHT, also enabling the attainment of thermal maps of the area of interest. These findings are a milestone on the road toward controlled magnetothermal therapies with minimal side effects.Ministerio de Ciencia, Innovacion y Universidades PID2019-106301RB-I00 PID2019-105195RA-I00Spanish Ministry of Economy and Competitiveness MAT2017-85617-R SEV-2016-0686Comunidad de Madrid (RENIM-CM - European Structural and Investment Fund) B2017/BMD-3867 NANOMAGCOST-CM P2018/NMT-4321Spanish Scientific Network HiperNano RED2018-102626-TEuropean Commission Horizon 2020 project NanoTBTech 801305CAM PEJ-2018-AI/IND-11245Comunidad de Madrid 2019-T1/IND-14014Juan de la Cierva Formacion scholarship FJC2018-036734-IEuropean Commission through the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant 797945Juan de la Cierva Incorporacion scholarship IJC2019-041915-IComunidad de Madrid 2018-T1/IND-1005AECC (Ideas Semilla 2019 project)European COST Action (MyWave) CA17115European COST Action (Nano2Clinic) CA1714

Multifunctional nanoparticles for hyperthermia, thermometry and fluorescenceimaging in the biological windows

Tesis Doctoral inédita cotutelada por la Universidade Federal de Alagoas de Brasil y la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de lectura: 17-12-2018In this thesis, the use of core/shell engineering for the synthesis of fluorescent nanoparticles (NPs) capable of operating as nanothermometers, nanoheaters and/or contrast agents for fluorescence imaging in small animal models is explored. The materials here studied – rare-earth (Nd3+, Yb3+, Tm3+ and/or Er3+) doped NPs and PbS/CdS/ZnS quantum dots (QDs) – presented emission and/or excitation bands in the so-called biological windows, where light penetration into tissues is maximal, allowing for ex vivo and in vivo applications. It was demonstrated that the spatial separation between the rare-earth ions, achieved by the core/shell nano-engineering, resulted not only in a considerable improvement on the values of thermo-optical parameters such as the light-heat conversion efficiency and the relative thermal sensitivity, but also on a multi-functionality of the nanosystems. As a consequence, innovative applications in nanothermometry were successfully accomplished when developing this thesis. Among those applications, one can mention: the study in real time of the thermal dynamics of an in vivo tissue, the detection and monitoring of cardiovascular diseases and the recording of in vivo thermal images and videos at a subcutaneous level by means of a ratiometric approach. The results here presented open up avenues for new diagnosis and control techniques that can revolutionize the current methods found in biomedicin

New opportunities for light-based tumor treatment with an “iron fist”

The efficacy of photodynamic treatments of tumors can be significantly improved by using a new generation of nanoparticles that take advantage of the unique properties of the tumor microenvironmen

Quo vadis, nanoparticle-enabled in vivo fluorescence imaging?

The exciting advancements that we are currently witnessing in terms of novel materials and synthesis approaches are leading to the development of colloidal nanoparticles (NPs) with increasingly greater tunable properties. We have now reached a point where it is possible to synthesize colloidal NPs with functionalities tailored to specific societal demands. The impact of this new wave of colloidal NPs has been especially important in the field of biomedicine. In that vein, luminescent NPs with improved brightness and near-infrared working capabilities have turned out to be optimal optical probes that are capable of fast and high-resolution in vivo imaging. However, luminescent NPs have thus far only reached a limited portion of their potential. Although we believe that the best is yet to come, the future might not be as bright as some of us think (and have hoped!). In particular, translation of NP-based fluorescence imaging from preclinical studies to clinics is not straightforward. In this Perspective, we provide a critical assessment and highlight promising research avenues based on the latest advances in the fields of luminescent NPs and imaging technologies. The disillusioned outlook we proffer herein might sound pessimistic at first, but we consider it necessary to avoid pursuing "pipe dreams"and redirect the efforts toward achievable - yet ambitious - goalsThis work has been cofinanced by European Structural and Investment Fund and by the European Union’s Horizon 2020 FET Open program under grant agreement no. 801305 (NanoTBTech). E.X. is grateful for a Juan de la Cierva Formacion scholarship (FJC2018-036734-I). A.B. acknowl- ́ edges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. D.

Less is more: dimensionality reduction as a general strategy for more precise luminescence thermometry

Thermal resolution (also referred to as temperature uncertainty) establishes the minimum discernible temperature change sensed by luminescent thermometers and is a key figure of merit to rank them. Much has been done to minimize its value via probe optimization and correction of readout artifacts, but little effort was put into a better exploitation of calibration datasets. In this context, this work aims at providing a new perspective on the definition of luminescence-based thermometric parameters using dimensionality reduction techniques that emerged in the last years. The application of linear (Principal Component Analysis) and non-linear (t-distributed Stochastic Neighbor Embedding) transformations to the calibration datasets obtained from rare-earth nanoparticles and semiconductor nanocrystals resulted in an improvement in thermal resolution compared to the more classical intensity-based and ratiometric approaches. This, in turn, enabled precise monitoring of temperature changes smaller than 0.1 °C. The methods here presented allow choosing superior thermometric parameters compared to the more classical ones, pushing the performance of luminescent thermometers close to the experimentally achievable limits.publishe

LaF3 core/shell nanoparticles for subcutaneous heating and thermal sensing in the second biological-window

We report on Ytterbium and Neodymium codoped LaF3 core/shell nanoparticles capable of simultaneous heating and thermal sensing under single beam infrared laser excitation. Efficient light-to-heat conversion is produced at the Neodymium highly doped shell due to non-radiative de-excitations. Thermal sensing is provided by the temperature dependent Nd3+ → Yb3+ energy transfer processes taking place at the core/shell interface. The potential application of these core/shell multifunctional nanoparticles for controlled photothermal subcutaneous treatments is also demonstratedThis work was supported by the Spanish Ministerio de Economıa y Competitividad (MAT2013-47395-C4-1-R), by Brazilian Agencies: FINEP (Financiadora de Estudos e Projetos) through the Grant Nos. INFRAPESQ-11 and INFRAPESQ-12; CNPq (Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico) Grants INCT NANO(BIO)SIMES and Project Universal No. 483238/2013-9; CAPES (Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior) by means of the Project PVE No. A077/2013. Erving C. Ximendes is supported by a Ph.D. scholarship from CNPq and currently by the PVE A077/2013 Project by means of a Ph.D. sandwich program developed at the Universidad Autonoma de Madrid, Spain. Prof. Dr. Daniel Jaque is the PVE (Pesquisador Visitante Especial) of the Project No. A077/2013. Dr. K. U. Kumar is a post-doctoral fellow of this Project. Dr. Ueslen Rocha is supported by a Post Doctoral Fellowship grant PDE/CAPES at the Universidad Autonoma de Madrid-Spain through the Project No. 2108-14-

O GRUPO THE MANIFEST: (RE)INVENTANDO O HIP HOP

Nessa pesquisa é feito um estudo das identidades produzidas pelos discursos dos jovens que integram o grupo de Hip Hop The Manifest da cidade de Bagé (RS), cidade que ainda tem forte interferência de uma cultura cristã e do campo, que valoriza o esforço e as tradições. O Hip Hop tem como uma de suas características históricas os movimentos sociais de jovens negros e pobres que moravam nos guetos das cidades norte-americanas. Com a globalização o Hip Hop se espalhou pelo mundo e sofreu mudanças. Neste estudo buscou-se entender como se constituem as identidades desses sujeitos e seus discursos acerca do Hip Hop. Com base nas teorias foucaultianas e nos Estudos Culturais, foram analisados os regimes de verdade e governamentos presentes, se persistem práticas discriminatórias e excludentes em relação aos grupos que, originalmente, não se ajustavam aos padrões estabelecidos ou se esses grupos são absorvidos pelas novas configurações sociais e culturais criadas com a globalização. Na análise levou-se em conta as práticas discursivas e não discursivas, as regularidades e descontinuidades encontradas nas falas de cada jovem entrevistado. Os discursos dos sujeitos entrevistados indicaram descontinuidades quanto a compreensão das novas tecnologias como fator de visibilidade do Hip Hop. As continuidades aparecem quanto a necessidade de manter certas tradições do movimento e na valorização da dança como arte que permite aos sujeitos transgredirem os discursos preconceituo

o contributo da neurociência no estudo do comportamento criativo

Tese de mestrado, Educação artística, Universidade de Lisboa, Faculdade de Belas Artes, 2011This work will discuss and present the possible mind proceedings underlying the creative behaviour, revealed and measured by cognitive neuroscience. Human behaviour and creativity are cognitive neurosciences’ recent interests, which appropriate terms and concepts belonging to several areas, such as psychology and neuropsychology, thought as complementary instead of competitors. One of the goals of art education is the development of creativity. However, in order this to occur, by far more than cognitive aspects are needed. Recent efforts have been keeping their focus on the cognitive processes that might be important by expressing novelty and for the appropriate use of it in a particular context. Thereby intelligence as well as divergent thinking being those to have been selected an even to have obtained some exclusiveness by scientists. In the beginning of the twentieth century, there was a huge tendency to relate determined behaviours to specific brain areas, which now a days can be confirmed through fostered techniques of brain visualisation. This research implies some principles, such as plasticity, behaviour, personality, which interconnect with the creative manifestation of the subject. We intent to put in evidence its scientific basis through cognitive neuroscience. With this approach, we hope to dissipate the prejudice about creativity being a matter of geniuses, but instead that it belongs to our biological equipmen

Quem é louco que se apresente, aqui a loucura é ao vivo

Este trabalho é resultado de um percurso de dois anos no Programa de Residência Integrada Multiprofissional em Saúde Mental Coletiva, da Universidade Federal do Rio Grande do Sul. Contempla fundamentalmente uma experiência inovadora e singular, surgida em meio a pandemia de Covid-19, vivida no ano de 2020, exigindo da população afastamento social protetivo. Em meio ao “isolamento”, surge a proposta de uma interação com a cultura por meio das artes visuais, da música e da dança, o que gerou o prolongamento de nossos corpos pelas redes virtuais e a produção de um novo afeto protetor. Não o afastamento, mas a conexão artística. O trabalho segue uma narrativa diarista (narrativa na primeira pessoa) e documental (memória e história), que considera uma experiência vivida (relato de experiência). O trabalho, nesse sentido, documenta um componente de formação em ato, como se espera das residências em saúde, e um aprendizado do “sentir-com” e da “criação coletiva”, desde uma imposição imanente gerada nos corpos e afetos dos residentes. Verifica-se, por fim, que o trabalho socioassistencial, a atenção psicossocial e a intervenção artística traçam laços de vizinhança e intercessão, mostrando a importância de uma residência integrada e multiprofissional na formação para a promoção do cuidado em saúde mental e a procedência de um currículo que se faz em ato, junto ao caminhar das realidades vivas e demandantes.This work is the outcome of a two years journey undergoing the Federal University of Rio Grande do Sul’ residence program in collective mental health. It reflects an innovative and unique experience, lived during the Covid-19 pandemic, in 2020, that has required the whole world population to take preventive social distancing measures. The proposal of culture interaction based on visual art, music and dance, emerged during the peak of 2020’s social distancing period, allowing the creation of an extension of our physical bodies through virtual networks, producing new protective affection through the artistic connection. The work follows a daily documentation through a diary that registered the lived experiences. It documents a fieldwork component expected in health specialization studies, a knowledge of “feeling-with” and “collective creation” imposed through the imanence generated in residents’ bodies and feelings. Finally, this study draws intersections between social care work, psychosocial care and artistic mediation, highlighting the importance of an integrated and multi-professional experience based on an educational residency programme, which contributes to foster and raise an action based mental health care practice and curriculum

In Vivo Spectral Distortions of Infrared Luminescent Nanothermometers Compromise Their Reliability

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/full/10.1021/acsnano.9b08824Luminescence nanothermometry has emerged over the past decade as an exciting field of research due to its potential applications where conventional methods have demonstrated to be ineffective. Preclinical research has been one of the areas that have benefited the most from the innovations proposed in the field. Nevertheless, certain questions concerning the reliability of the technique under in vivo conditions have been continuously overlooked by most of the scientific community. In this proof-of-concept, hyperspectral in vivo imaging is used to explain how unverified assumptions about the thermal dependence of the optical transmittance of biological tissues in the so-called biological windows can lead to erroneous measurements of temperature. Furthermore, the natural steps that should be taken in the future for a reliable in vivo luminescence nanothermometry are discussed together with a perspective view of the field after the findings here reportedThis work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2016-75362-C3-1-R, MAT2017-83111R, and MAT2017-85617-R, by the Instituto de Salud Carlos III (PI16/00812), and by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM) and cofinanced by the European Structural and investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open programme (grant agreement No 801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265), and also COST action CA17140. Y. Shen acknowledges a scholarship from the China Scholarship Council (No. 201806870023