Orientador: Ana Paula Risifni Alves Claro / Resumo: Infecção bacteriana sempre foi uma grande preocupação para medicina, principalmente devido a capacidade de adaptação de bactérias, e consequente aparecimento de cepas resistentes aos medicamentos convencionais. Como alternativa a esta problemática, estudos vem comprovando a eficácia de íons metálicos, no combate a diferentes tipos de microrganismos. Dentre metais com propriedade bactericida, há o gálio, elemento com interessante conjunto de propriedades que possibilitaram seu uso em tratamentos terapêuticos, entretanto sua ação bactericida ainda se encontra pouco explorada na literatura. Como forma veiculação deste metal, escolheu se a polidopamina, um polímero baseado em compostos presentes na composição de moluscos, os quais lhe confere m interessantes propriedades de adesão em diferentes superfícies e capacidade de ancoragem de íons ou moléculas. Com base nas informações expostas, a presente dissertação tem por objetivo produzir partículas de polidopamina com incorporação de gálio para aplicação biomédica . Para isso, inicialmente o polímero foi sintetizado a partir da polimerização do hidrocloreto de dopamina em ambiente alcalino, com pH ajustado em 9,0 a temperatura ambiente e com agitação magnética. Em seguida o material foi centrifuga do e seco. Em fase posterior, a incorporação do gálio se deu a partir da dissolução de nitrato de gálio na presença das partículas previamente produzidas, sendo mantido em solução por 18 horas. O material resultante foi novamente centrifu... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Orientador: Aldo Eloizo Job / Resumo: As vantagens do uso de dispositivos ópticos na área das ciências da vida são amplamente exploradas, especialmente para o diagnóstico médico e protocolos de tratamento em uma prática de cuidados de saúde. Além disso, alguns pesquisadores têm atraído muita atenção ao desenvolvimento de materiais biocompatíveis e vestíveis para melhorar a segurança de dispositivos médicos, bem como para estabelecer novos procedimentos para monitorar a resposta de terapia e diagnóstico clínico. O presente trabalho tem como objetivo desenvolver uma membrana biocompatível-luminescente não invasiva para reduzir os erros mais comuns relatados em fototerapia convencional de luz azul para icterícia neonatal. Dentre estes erros destacam-se: intensidade de irradiância que chega ao recém-nascido bem como seu posicionamento frente a fonte de radiação e qualidade das lâmpadas dos aparelhos fototerápicos. Neste contexto, a membrana foi confeccionada como um filme de sensor de luz azul, fluorescente e colorimétrico a partir de polímeros: poli [2-metoxi, 5-(2'etilhexyloxy)-pfenilenovileno (MEH-PPV) em uma matriz de borracha natural. Para tal, as membranas de borracha natural (BN) foram obtidas utilizando o látex, extraído das árvores Hevea brasiliensis (clone RRIM 600), por casting, com posterior tratamento térmico em estufa. Em seguida, também por casting, a solução de MEH-PPV/BN, razão igual a 4000, foi depositada na membrana BN para fazer uma camada fina de material luminescente. A membrana de MEH-PPV/BN fo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The advantages of optical devices in the life sciences are widely exploited, especially for medical diagnosis and treatment protocols in a health care practice. In addition, some researchers have attracted much attention to development flexible and biocompatible materials to improve security of medical devices, as well as to establish new procedures for monitoring therapy response and clinical diagnosis. The present paper aims to develop a new noninvasive biocompatible-luminescent membrane to reduce the most common user errors with conventional blue-light phototherapy of neonatal jaundice. The membrane was design based on a polymer-based fluorescent and colorimetric blue-light sensor film. This material was based on poly[2-methoxy,5-(2'etilhexyloxy)-p-fenilenovileno (MEH-PPV) in a natural rubber matrix. Natural rubber membranes (BN) were obtained using latex from Hevea brasiliensis trees (clone RRIM 600) by casting, with the time and temperature of thermal treatment fixed on 65°C for 10h. Then, also by casting, MEH-PPV/NR solution, ratio equal to 4000, was deposited on NR membrane for make thin-layer of luminescent material. The MEH-PPV/NR membrane was submitted to the same conditions used for neonatal hyperbilirubinemia treatment (Blue light phototherapy, 40 µW/m2 /nm, 460nm). The proprieties of membranes were characterized by optical (UV-Vis, PL) and infrared (FTIR) spectroscopy confocal microscopy (MC), scanning electron microscopy (SEM) and atomic force microscopy (AFM) a... (Complete abstract click electronic access below) / Doutor

L'objectif principal de ce travail de thèse étant la préparation de nanovecteurs biocompatibles, nous avons mis au point des systèmes catalytiques exempts de métal pour polymériser les différents monomères préparés dérivés de l’acide diméthylmalique. En présence de ces systèmes catalytiques, la polymérisation anionique par ouverture de cycle (aROP) se déroule de manière contrôlée avec une cinétique plus rapide que celle réalisée en présence d’autres organo-catalyseurs déjà décrit dans la littérature. Nous avons ainsi synthétisé trois homopolymères hydrophobes et deux familles de copolymères di-blocs amphiphiles ayant différentes balances hydrophiles/hydrophobes. Des nanoparticules (NPs) ont été préparées par nanoprécipitation à partir des homopolymères hydrophobes et des copolymères à blocs amphiphiles. La taille des NPs varie entre 30 et 170 nm avec de faibles dispersités (PDI ≤ 0,23) et ayant une très bonne stabilité à 4°C et à 37°C. Des études de cytotoxicité in vitro sur la lignée cellulaire d'hépatome HepaRG ont mis en évidence que toutes les NPs ont une faible toxicité à des concentrations inférieures à 3 μM. En parallèle, une sonde fluorescente, le DiR, a été encapsulée dans les NPs lors de la nanoprécipitation sans affecter les caractéristiques et la stabilité des NPs correspondantes. Enfin, des études in vitro utilisant ces NPs chargées en DiR ont montré que ces dernières étaient effectivement captées par les cellules HepaRG avec différents pourcentages de captation. / The main objective of this PhD thesis being the preparation of biocompatible nanovectors, we have set up metal-free catalytic systems to polymerize various prepared monomers derived from dimethylmalic acid. Using such catalytic systems, the anionic ring opening polymerization (aROP) proceeds in a controlled manner with faster kinetics compared to the organo-catalysts already reported in the literature. Three hydrophobic homopolymers and two families of amphiphilic block copolymers with different hydrophilic/hydrophobic balances have been therefore synthesized. Nanoparticles (NPs) have been prepared by nanoprecipitation of these hydrophobic homopolymers and amphiphilic block copolymers. The size of the NPs ranges from 30 to 170 nm with low dispersity values (PDI ≤ 0.23) and high stability at 4°C and 37°C. In vitro cytotoxicity studies on HepaRG hepatoma cell line have highlighted that all the NPs have low toxicity at concentrations lower than 3μM. In parallel, NPs were loaded with the fluorescent probe DiR without altering the characteristics and the stability of the corresponding DiR loaded NPs. Finally, in vitro studies using NPs loaded with DiR have shown that HepaRG cells effectively uptake the NPs in different percentages of uptake.

In this dissertation, tribo-corrosion behavior of several single-phase and multi-phase high entropy alloys were investigated. Tribo-corrosion of body centered cubic MoNbTaTiZr high entropy alloy in simulated physiological environment showed very low friction coefficient (~ 0.04), low wear rate (~ 10-8 mm3/Nm), body-temperature assisted passivation, and excellent biocompatibility with respect to stem cells and bone forming osteoblast cells. Tribo-corrosion resistance was evaluated for additively manufactured face centered cubic CoCrFeMnNi high entropy alloy in simulated marine environment. The additively manufactured alloy was found to be significantly better than its as-cast counterpart which was attributed to the refined microstructure and homogeneous elemental distribution. Additively manufactured CoCrFeMnNi showed lower wear rate, regenerative passivation, less wear volume loss, and nobler corrosion potential during tribo-corrosion test compared to its as-cast equivalent. Furthermore, in the elevated temperature (100 °C) tribo-corrosion environment, AlCoCrFeNi2.1 eutectic high entropy alloy showed excellent microstructural stability and pitting resistance with an order of magnitude lower wear volume loss compared to duplex stainless steel. The knowledge gained from tribo-corrosion response and stress-corrosion susceptibility of high entropy alloys was used in the development of bio-electrochemical sensors to sense implant degradation. The results obtained herewith support the promise of high entropy alloys in outperforming currently used structural alloys in the harsh tribo-corrosion environment.

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Thesis advisor: Jia Niu / O-Sulfation is an important chemical code existing widely in nature, participating in a variety of biological activities including immune response, hemostasis, hormone regulation, cell signaling, and viral invasion. The heterogeneous nature, high polarity with negative charge, and the chemical lability of the sulfate modification have created significant challenges in the synthesis and structure-function studies of O-sulfated biomolecules. It is therefore highly desirable to achieve caging and selective release of the O-sulfated biomolecules. Inspired by sulfur (VI) fluoride exchange reaction, our group developed a series of general approaches to caged O-sulfated biomolecules and their selective deprotection. First, an O-sulfation strategy is developed by coupling aromatic fluorosulfate with silylated target molecules. Scalable synthesis was demonstrated on monosaccharides, disaccharides, amino acid, and steroid. Selective hydrolytic and hydrogenolytic removal of the aryl masking groups yielded the corresponding O-sulfated products in excellent yields. Furthermore, a complete knowledge gap was noted in biocompatible caging of sulfate. With the rational design and systematic optimizations, we discovered that fluorosulfotyrosine in peptides and proteins was an ideal precursor for sulfotyrosine (sY), which can be efficiently converted into the anionic active form by hydroxamic acid activators under physiologically relevant conditions. Photocaging the hydroxamic acid activators further allowed for light-controlled activation of functional sulfopeptides. This system featuring fast kinetics, high selectivity, excellent robustness, and on-demand release provides a valuable tool for probing functional roles of sulfation in the peptides and proteins. / Thesis (PhD) — Boston College, 2023. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13587号 / 論医博第2307号 / 新制||医||1070(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 森本 尚樹, 教授 伊達 洋至 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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De nouveaux glycopolymères amphiphiles en peigne de type dextrane-g-poly(méthacrylate de méthyle) ont été obtenus via une polymérisation radicalaire contrôlée par transfert d’atome (ATRP). Pour contrôler les paramètres macromoléculaires de ces glycopolymères potentiellement biocompatibles et en partie biodégradables, la stratégie de synthèse « grafting from » a été sélectionnée et appliquée selon deux voies de synthèse. La première voie comporte quatre étapes : acétylation partielle des fonctions hydroxyle du dextrane ; introduction des groupements amorceurs d’ATRP ; ATRP contrôlée du méthacrylate de méthyle dans le diméthylsulfoxyde ; hydrolyse des groupements acétate dans des conditions douces. La seconde voie de synthèse permet d’obtenir ces glycopolymères en seulement deux étapes : introduction directe des groupements amorceurs d’ATRP sur le dextrane ; ATRP contrôlée du méthacrylate de méthyle dans le diméthylsulfoxyde. Des études détaillées de chaque étape ont permis à la fois d’estimer la longueur de la chaîne de dextrane et d’assurer le contrôle de l’architecture des glycopolymères (nombre et longueur des greffons). Des études préliminaires par tensiométrie interfaciale ont permit d’évaluer le caractère tensioactif de ces glycopolymères / Synthesis of the new comb-like amphiphilic glycopolymer dextran-g-poly(methyl methacrylate) was obtained thanks to an Atom Transfert Radical Polymerization (ATRP). In order to control the macromolecular parameters of these biocompatible and partly biodegradable glycopolymers, the “grafting from” strategy was applied using two different multi-step pathways. The first one is composed of four steps: partial acetylation of dextran hydroxyl groups; introduction of initiator groups convenient for ATRP; ATRP of methyl methacrylate in dimethylsulfoxide; acetyl group deprotection under mild conditions. The second pathway allows us to obtain such glycopolymers in only two steps: direct introduction of the same initiator groups onto the dextran chain and subsequent ATRP of methyl methacrylate in dimethylsulfoxide. Throughout the synthesis, detailed studies of each step enabled us to estimate the length of the dextran backbone and to assure the control of copolymer architecture in terms of graft number and graft length. Preliminary interfacial tension measurements highlighted the surfactant properties of such glycopolymers