Rozprawy doktorskie na temat „Nanoflowers”

Un immense intérêt est porté sur les nanostructures métalliques anisotropes d’or (AuNFs) qui s’explique par les propriétés uniques qu’elles procurent et qui peuvent servir dans divers domaines, notamment dans le biomédicale. On cherche à maitriser leurs propriétés optiques liées aux oscillations collectives d’électrons de surface appelées plasmons. Elles possèdent une bande de résonance plasmonique localisée de surface (LSPR, comme localized surface plasmon resonance) située dans le rouge - proche infrarouge (> 600 nm). Leur capacité d’interagir avec la lumière rouge - proche IR (fenêtre optique biologique) les rend intéressantes en tant qu’agent d’imagerie optique et opto-acoustique. Dans le cas particulier de la diffusion Raman exaltée de surface (SERS, comme surface-enhanced Raman scattering), les AuNFs sont capables de procurer les zones d’exaltation appelées « hot spots » dans les jonctions entre leurs pétales. Ainsi, on peut les utiliser comme substrat SERS sans avoir besoin de les agréger, à la différence des nanosphères d’or. Le protocole de synthèse des AuNFs que nous avons développé est rapide, en une seule étape et n’utilise qu’un nombre réduit de réactifs connus qui sont peu ou pas toxiques. De plus, notre protocole permet de contrôler les caractéristiques des AuNFs telles que leur taille et la position de leur bande LSPR, entre 600 et 900 nm. Afin de garantir une stabilité colloïdale dans des milieux divers, nous avons enrobé nos AuNFs avec des polymères biocompatibles (alginates, chitosan, Pluronics, PVP et PEG) ou les avons encapsulées dans une matrice de silice. Les substrats colloïdaux à base de ces AuNFs enrobées d’enveloppes biocompatibles ont ainsi montré leur potentiel pour procurer l’effet SERS sans agrégation et permettre l’analyse ultrasensible de petits chromophores (comme le Bleu de Nil). De plus, nos résultats montrent que ces nouveaux substrats sont capables de délivrer une charge de molécules dans des cellules cancéreuses. Ainsi, ils semblent prometteurs en tant qu’agents théranostiques, applicables non seulement en SERS, mais également en imagerie optique ou opto-acoustique et en thérapie
A huge attention is paid on anisotropic gold metal nanostructures (AuNFs) because of the unique properties they can provide in various fields, in particular the biomedical applications. We are trying to control their optical properties related to the collective oscillations of surface electrons called plasmons. They have a localized surface plasmon resonance band (LSPR) located in the red - near infrared (> 600 nm). Their ability to interact with red light - near IR (optical biological window) makes them interesting as optical and optoacoustic imaging agents. In the specific case of the surface-enhanced Raman scattering (SERS), AuNFs are able to provide enhancement zones called "hot spots" in the junctions between their petals. Thus, they can be used as SERS substrates without the need to be aggregated, unlike for gold nanospheres. The protocol to synthesize AuNFs that we developed is fast, in one-step and uses only a small number of known reagents that are low or non-toxic. In addition, our protocol allows us to tune the characteristics of the AuNFs such as their size and the position of their LSPR band, between 600 and 900 nm. In order to guarantee their colloidal stability in various media, we have coated our AuNFs with biocompatible polymers (alginates, chitosan, Pluronics, PVP and PEG) or encapsulated them in a silica matrix. Colloidal substrates based on these AuNFs coated with biocompatible envelopes have thus shown their potential to provide the SERS effect without aggregation and allow the ultra-sensitive analysis of small chromophores (such as Nile Blue). In addition, our results show that these new substrates are able to deliver a cargo of molecules to the cancer cells. Thus, they seem promising as theranostic agents, applicable not only in SERS, but also in optical or optoacoustic imaging and therapy

Dans les domaines de l’imagerie médicale et la thérapie, l’utilisation des nanoparticules est spécialement attrayante et prometteuse. Il est possible de concentrer dans une même particule plusieurs fonctions complémentaires comme la détection, le ciblage mais aussi la thérapie. Cette multifonctionnalité présente de nombreux avantages, et favorise le développement de nanoparticules pour une thérapie ciblée et guidée par l’imagerie.C’est dans ce contexte d’intense activité centrée sur le développement des nanoparticules pour les applications médicales (imagerie et/ou thérapie) que s’est déroulé mon travail de thèse qui s’inscrit dans la continuité des travaux de Christophe Alric et de Pierre Hugounenq. Ils ont développé respectivement des nanoparticules d’or multifonctionnelles (Au@DTDTPA) et des nanofleurs d’oxyde de fer (γ-Fe2O3).Les nanoparticules d’or (Au@DTDTPA) présentent un effet radiosensibilisant et se comportent comme agent de contraste pour l’IRM (après marquage par Gd3+ rendu possible par les propriétés chélatantes de la couche organique DTDTPA) ou comme radiotraceurs après radiomarquage (le DTDTPA forme des complexes stables avec 99mTc et 111In). Le caractère superparamagnétique des nanofleurs d’oxyde de fer confèrent à ces objets la capacité à rehausser le contraste négatif des images et à induire un échauffement sous l’action d’un champ magnétique alternatif de haute fréquence.L’objectif principal de ma thèse consistait à assembler ces deux types de nanoparticules afin de créer un objet nanométrique combinant les propriétés complémentaires des nanoparticules d’or et des nanofleurs d’oxyde de fer. Dans un premier temps, les conditions optimales de greffage des nanoparticules d’or sur les nanofleurs ont été déterminées. Nous avons montré que de tels agents présentaient après injection intraveineuse une biodistribution adaptée comme le révèlent les images acquises en IRM (grâce aux propriétés magnétiques des nanofleurs) et en TEMP (grâce au radiomarquage de la couche des nanoparticules d’or). En outre ces objets présentent un caractère radiosensibilisant qui est mieux exploité que celui des nanoparticules d’or entrant dans la composition de ces nanofleurs dorées. Associé au pouvoir chauffant des nanofleurs, le pouvoir radiosensibilisant des nanofleurs dorées a conduit à une forte inhibition de la croissance tumorale quand le traitement de rats portant un mélanome combine hyperthermie magnétique et radiothérapie après injection intratumorale des nanofleurs dorées.En conclusion, le travail réalisé au cours de cette thèse a mis en évidence l’intérêt de combiner les nanoparticules d’or et les nanofleurs d’oxyde de fer pour traiter des tumeurs solides par thérapie guidée par imagerie
In the fields of medical imaging and therapy, the use of nanoparticles is especially attractive and promising. It is possible to concentrate in the same particle several complementary functions such as detection, targeting but also therapy. This multifunctionality has many advantages and promotes the development of nanoparticles for targeted therapy and guided by medical imaging.It is in this context of intense activity focused on the development of nanoparticles for medical applications (imaging and/or therapy) that my thesis work was carried out which is in continuity with the work of Christophe Alric and Pierre Hugounenq. They developed multifunctional gold nanoparticles (Au@DTDTPA) and iron oxide nanoflowers (γ-Fe2O3), respectively.The gold nanoparticles (Au @ DTDTPA) exhibit a radiosensitizing effect and behave as a contrast agent for MRI (after labeling with Gd3 +, made possible by the chelating properties of the organic layer DTDTPA) or radiotracers after radiolabelling (DTDTPA forms stable complexes with 99mTc and 111In). The superparamagnetic nature of the iron oxide nanoflowers gives these objects the ability to enhance the negative contrast of the images and to induce heating under the action of an alternating magnetic field of high frequency.The main objective of my thesis was to assemble these two types of nanoparticles in order to create a nanometric object combining the complementary properties of gold nanoparticles and iron oxide nanoflowers. In a first step, the optimal conditions for grafting gold nanoparticles on the nanoflower were determined. We have shown that, after intravenous injection, these agents exhibit a suitable biodistribution, as revealed by MRI images (thanks to the magnetic properties of nanoflowers) and SPECT (thanks to the radiolabeling of the gold nanoparticle layer). Moreover, these objects have a radiosensitizing character which is better exploited than that of the gold nanoparticles in the golden nanoflowers. Associated with the heating power of nanoflower, the radiosensitizing potential of golden nanoflowers has led to a strong inhibition of tumor growth when the treatment of rats carrying melanoma combines magnetic hyperthermia and radiotherapy after injection of golden nanoflower.In conclusion, the work carried out during this thesis has highlighted the value of combining gold nanoparticles and iron oxide nanoflowers to treat solid tumors by imaging-guided therapy

Nanopartículas de ouro têm mostrado enorme potencial de aplicação em modalidades diagnósticas e terapêuticas fotoativadas. Em especial, nanoestruturas de ouro anisotrópicas ramificadas apresentam excelente desempenho atuando tanto como contrastes de imagens fotoacústicas, quanto como agentes ativos para terapias fototérmicas de câncer. Apesar dos avanços nas suas rotas de síntese, o desenvolvimento dessas nanoestruturas de forma simples e reprodutível ainda é desafiador. O presente trabalho visou o desenvolvimento de nanopartículas de ouro anisotrópicas ramificadas, ou nanoflores, que sejam fotoativas no infravermelho-próximo para a terapia e diagnóstico de câncer. Em particular, buscou-se o desenvolvimento de uma síntese simples para sua obtenção, assim como a verificação de sua atuação como agente de contraste fotoacústico e como agente ativo para hipertermia de tumores. Para tanto, desenvolveu-se uma síntese in situ que permitiu a obtenção de nanoflores monodispersas com tamanho e propriedades ópticas controláveis. Através da variação de aspectos da síntese, como a temperatura e a concentração de ouro, foi possível sintonizar a atividade óptica das partículas entre 590 e 960 nm. Sua formação foi confirmada por microscopia eletrônica de varredura, espalhamento de luz dinâmico e espectroscopia UV-visível. As partículas apresentaram boa estabilidade de suas características físico-químicas por dois meses e meio. Ainda, as nanoflores se mostraram estáveis, também, quando suspensas em meio de cultura, sob irradiação de lasers, e quando mantidas a temperatura corpórea por longos intervalos. Sua resposta fotoacústica foi caracterizada, apresentando sinais significativos e permitindo a obtenção de imagens claras de sua localização, mesmo em baixas concentrações. Testes realizados em cultura de células mostraram que as nanoflores foram eficazes na hipertermia de uma linhagem de hepatocarcinoma de rato (HTC), ao mesmo tempo que não apresentaram sinais de toxicidade a uma linhagem de fibroblastos de camundongos (FC3H). Esses resultados revelam uma possibilidade simples de fabricação de nanoestruturas de ouro anisotrópicas ramificadas, que podem servir como uma plataforma promissora para o diagnóstico e terapia do câncer.
Gold nanoparticles have shown enormous potential of application in photodiagnostic and in phototherapeutic procedures. Notably, branched anisotropic gold nanostructures present distinguished performance acting as contrast agents of photoacoustic images and as active agents for photothermal therapies for cancer. Despite advances in their synthesis routes, the growth of these nanostructures in a simple and reproducible way is still challenging. The present study was aimed at developing branched anisotropic gold nanoparticles, coined nanoflowers, that are photoactive in the near-infrared for therapy and diagnosis of cancer. In particular, we sought to develop a simple synthesis route, as well as to verify its application for both, as photoacoustic contrast agents and as active agents for tumor hyperthermia. An in situ synthesis was developed which allowed the development of monodisperse nanoflowers with controllable size and optical properties. Through variations of certain aspects of this procedure, such as temperature and gold ions concentration, it was possible to tune the optical activity of the particles between 590 and 960 nm. The nanostructure morphology was confirmed by scanning electron microscopy, dynamic light scattering and UV-visible spectroscopy. The particles exhibited consistent physicochemical characteristics and good stability for two and a half months. Furthermore, the nanoflowers were also stable when suspended in cell culture medium, under laser irradiation and when maintained at body temperature for long intervals. Its photoacoustic response was characterized, presenting significant responses and generating clear images of its location, even at low concentrations. In vitro tests revealed that these nanoflowers were effective therapeutic agents for photothermal therapy of a rat hepatocarcinoma (HTC) lineage, while showing no signs of toxicity to mouse fibroblast (FC3H) cell line. These results reveal a simple procedure of synthesizing branched anisotropic gold nanostructures, which can serve as a promising platform for cancer diagnosis and therapy.

The encapsulation of devices sensitive to moisture is necessary to prolong lifetimes under adverse environmental conditions. Therefore, quantifying moisture flow is important in design and verification of the encapsulations. Gaseous flows have been studied after Knudsen’s paper appeared in 1909, with one important exception: water vapour. A recent unexpected finding from Holt et al. concerned ultra-fast water and air flows in carbon nanotubes. While Gruener and Huber did not obtain ultra-fast nitrogen flows in silicon nanotubes. This leaves us to concern main effective factors for flows in tubes. We use a theory of extended Navier-Stokes equations, having one equation for all flow regimes with an empirical parameter (Cha and McCoy theory), for predicting flow rates of nitrogen and water vapour through a 25 μm diameter silica glass cylindrical tube under isothermal condition. We measure nitrogen flow rates through microtubes across a wide range of Knudsen number (0.0048 ~ 12.4583) using a two-chamber method. We find that the nitrogen flow obeys the Cha and McCoy theory with values of the tangential momentum accommodation coefficient (TMAC) α= 0.91 at small Kn and α close to one at large Kn, consistent with the redefinition of α by Arya et al. We obtain fast transport of water vapour compared to the predictions from the Cha and McCoy theory over a range of pressures using the two-chamber method and a mass loss method. We attribute the excess flows to: (1) a thin adsorbed layer of chain-like water on the walls reducing the TMAC at low pressures; (2) liquid or two-phase flow appearing for inlet pressure close to saturation pressure. A theory for TMAC is developed based on the Langmuir adsorption. We measure interdiffusive flow rates of water vapour in atmospheric air for the first time using the mass loss method and compare experimental results with ideal gas interdiffusive flow theory. We find interdiffusive flows of water vapour in air agree with the theory except for the case where water vapour partial pressures are close to the saturation pressure. Liquid or two-phase flow causes an enhancement of the interdiffusive flow by up to three orders of magnitude. Using the available theories we predict the dominant flow types as a function of channel diameter and make recommendations on the moisture hermeticity testing in devices.

La radiothérapie est utilisée pour 50% des traitements contre le cancer. Cependant, sa mise en œuvre est limitée par la tolérance des tissus sains. De nouvelles stratégies associant nanomédecine et radiothérapie anticancéreuse ont été proposées il y a une dizaine d'années pour améliorer les performances des traitements. Un intérêt croissant est apparu pour les nanoparticules (NP) de Z élevé faites de métal en tant que radio-amplificateurs potentiels, pour augmenter les effets des radiations,Dans la première partie de mon travail, une méthode de radiolyse efficace et unique a été optimisée pour produire en une seule étape, de petites NPs de platine PEGylées dispersées dans une solution stérile, avec un rendement de production de 100%. Ces NP amplifient les effets des rayonnements comme les rayons γ et en particulier les faisceaux de particules. Cependant, la fonctionnalisation de surface de ces NP revêtues de PEGOH est difficile. Dans une deuxième étape, la même méthode de radiolyse a été utilisée pour produire d'autres NP à base de platine enrobées de PEG diamine. Ce revêtement permet de greffer diverses molécules telles que des marqueurs fluorescents, des médicaments ou des radionucléides. Ces particules PEGylées s'agrègent pour donner une forme de nanofleur. Elles peuvent être lyophilisées, ce qui garantit un stockage long et facile. Après caractérisation physico-chimique, leur efficacité en tant que radio-amplificateur a été évaluée in vitro. Des expériences à l'échelle moléculaire utilisant des plasmides comme biosondes moléculaires ont montré que ces NP amplifient l'induction de biodommages complexes. Nous avons attribué l'amplification de ces dommages aux processus physico-chimiques.En outre, la compatibilité sanguine des NP administrés par voie intraveineuse est également cruciale pour leur utilisation en nanomédecine. L'interaction avec les protéines en particulier peut provoquer des effets nocifs potentiels. Par conséquent, la caractérisation de l'impact des NP sur les protéines sanguines est une première étape dans la prévention de la toxicité et des effets indésirables. La deuxième partie de mon travail était consacrée au développement d'une nouvelle méthode multiparamétrique pour caractériser les changements structurels et de stabilité de l'albumine sérique humaine lors de l'interaction avec des nanoagents. Il a ainsi été constaté que les NP à base de gadolinium (AGuIX®) et les NP à base de platine ne se lient pas aux protéines. Fait intéressant, ils stabilisent la structure des protéines en raison d'un mécanisme d’hydratation.Enfin, l'utilisation des NP comme agents de contrastes multimodaux pour sonder la biodistribution in vivo et la pharmacocinétique a été explorée dans la troisième partie de ma thèse. Les NP de platine se sont révélées non seulement des radio-amplificateurs efficaces mais, grâce à leur coefficient d'atténuation des rayons X élevé, également un agent de contraste potentiel pour l'imagerie par tomodensitométrie (TDM). Plus intéressant encore, les NP à terminaison amine développées dans mon travail ont été fonctionnalisées avec succès avec des radionucléides. Cela a ouvert l'opportunité de les observer par imagerie par tomographie par émission de positons (TEP). Les expériences préliminaires de biodistribution ont montré une clairance hépatique et une accumulation des NP dans la tumeur persistant après plusieurs jours.En conclusion, les principaux résultats de mon travail comprennent l'optimisation d'une méthode rapide et efficace pour produire facilement et rapidement des solutions stériles de radio-amplificateurs multimodaux à base de platine qui peuvent également être détecté par TDM, TEP et fluorescence. De plus, il comprend le développement d'une nouvelle façon d'évaluer l'impact des NP sur les protéines sanguines avant les tests in vivo. Ces deux réalisations devraient contribuer à renforcer la stratégie combinant nanomédecine et radiothérapies
Radiotherapy is used for 50% of the cancer treatments. However, its implementation is limited by the tolerance of healthy tissues. New strategies combining nanomedicine and cancer radiation therapy have been proposed a decade ago to improve the performances of the treatments. Hence, a growing interest appeared for high-Z metal-based nanoparticles (NPs) as potential radio-enhancers, to amplify the effects of radiations.In the first part of my work, an efficient and unique radiolysis method was optimized to produce in one step, small, PEGOH-coated platinum NPs dispersed in a sterile solution, with 100% production rate. These NPs are good radio-enhancers, they amplify the radiation effects of γ-rays and particularly particle beams. However, further surface functionalization of these NPs coated with PEGOH is challenging. In a second step, the same radiolysis method was used to produce other platinum-based NPs coated with PEG diamine. This coating allows grafting of various molecules such as fluorescent markers, drugs or radionuclides. These particles aggregate with a shape of nanoflowers. They can be lyophilized, which ensures long and easy storage, and facile reconstitute with different biological buffers. After physico-chemical characterization, their efficiency as radio-enhancers has been evaluated in vitro. Molecular scale experiments using plasmids as molecular bioprobes showed that these NPs amplify the induction of complex biodamage. We ascribed the amplification of the damage to the activating radiation induced physico-chemical processes.Moreover, blood compatibility of NPs when administered intravenously, is also crucial for their use in nanomedicine. The interaction of NPs with proteins especially, can cause potential harmful effects. Hence, the characterization of the impact of NPs on blood proteins, is a first step in the prevention of adverse effects. The second part of my work was dedicated to the development of a new multiparametric method to characterize the structural and stability changes of human serum albumin upon interaction with nanoagents. It was found that gadolinium-based NPs (AGuIX) and platinum-based NPs do not bind to proteins. Interestingly, they stabilize the protein structure due to preferential hydration mechanism. Finally, the use of NPs as multimodal contrasts agents to probe in vivo biodistribution and pharmacokinetic, was explored in the third part of my thesis. Platinum NPs were found to be not only efficient radio-enhancers but, thanks to their high x-ray attenuation coefficient, also potential contrast agent for computed tomography (CT) imaging. More interestingly, the amine-terminated NPs developed in my work were successfully functionalized with radionuclides. This opened an opportunity to observe them by positron emission tomography (PET) imaging, The preliminary biodistribution experiments performed with CT and PET techniques showed hepatic clearance and accumulation of the NPs in the tumor after several days.In conclusion, the major outputs of my work include the optimization of a rapid and efficient method to easily and rapidly produce sterile solutions of multimodal platinum-based radio-enhancers which can be detected by CT, PET and fluorescence imaging. Moreover, it includes the development of a new way to evaluate the impact of NPs on blood proteins prior to in vivo tests. These two achievements will hopefully contribute to boost the strategy of combining nanomedicine and radiation therapies

碩士
國立成功大學
化學工程學系碩博士班
97
Iron phosphide nanorods and nanoflowers with size distributions were prepared by the multiple injections of organometallic precursor into hot surfactants via the thermal decomposition. The injections of iron pentacarboxyl (Fe(CO)5) dissolved in trioctylphosphine (TOP) into the mixture of trioctylphosphine (TOP), didodecyldimethylammonium bromide (DDAB), and spherical Fe3O4 seeds (~5.5nm) at 300oC, under argon atmosphere. Nanorods, analyzed through scanning electron microscope (SEM) and transmission electron microscope (TEM), with different aspect ratios from 4 to 30 can be prepared by using multiple injections under constant total reactant concentration and reaction time, and the increasing number of injections with the increase of aspect ratios. The size of nanoflowers also increases with the increasing number of injections. Besides,nanorods assembled at TEM grids caused by the surface tension of surfactants probably. Furthermore, the effect of reactant concentration, reaction time and temperature on the synthesis of nanorods was discussed comprehensively. X-ray diffractometer spectrometer (XRD) and superconducting quantum interference device (SQUID) were used to characterize the crystallization and magnetization of the iron phosphide nanorods according to the effect of morphology of the rods. Finally, we presumed a reasonable growth mechanism and determined the magnetism of nanorods, and identified the blocking temperature (TB) of the rods as a function of the length of the rods. Fe2P nanoparticles were prepared from Fe3O4 seeds via multiple injections and seed-mediated growth successfully. Compared with the past syntheses, it’s more alternative and effective on our study to control the shape and size distributions of particles in one synthetic process, and more potential on researches and applications of magnetic properties.

RESUMO: O cérebro é particularmente vulnerável ao stress oxidativo, uma vez que tem um elevado consumo de oxigénio que leva à produção de espécies reativas de oxigénio (ERO) e, simultaneamente, expressa uma baixa quantidade de enzimas antioxidantes. Enquanto a maioria dos tratamentos para o stress oxidativo se focam na eliminação das ERO, o mimetismo celular, que inclui reatores que podem incorporar várias entidades ativas, é considerado um novo modelo de tratamento eficiente e durador. Por exemplo, o consumo de ERO produzidas em excesso pode ser alcançado através da utilização da enzima superóxido dismutase (SOD) e de nanoflores de óxido de manganês. Este trabalho teve como objetivo o desenvolvimento de microreatores com capacidade de mimetizar as características celulares antioxidantes, de modo a prevenir o stress oxidativo induzido por H2O2 e lipopolisacárido (LPS) na linha celular SH-SY5Y de neuroblastoma humano e em culturas primárias mistas, respetivamente. SOD encapsulado em lipossomas (LSOD) e nanoflores foram sintetizados e caracterizados física- e cataliticamente. Microreatores foram construídos a partir dum núcleo de poliestireno, incorporando nanoflores ou nanoflores+LSOD como entidades ativas, e com deposição electroestática de camadas intermédias de polidopamina e poli-L-lisina. Quer as nanoflores, quer os microreatores, demonstraram atividade de SOD e catalase. O LSOD mostrou atividade baixa de SOD, que foi anulada pela incorporação destes no microreactor. Enquanto as nanoflores livres mostraram altas taxas de toxicidade na linha celular SH-SY5Y, quando incorporadas nos microreactores, estes mostraram baixos níveis de toxicidade direta e inibição de proliferação na linha celular. Os microreactores foram capazes de reverter parcialmente a viabilidade da linha celular tratada com H2O2, no entanto induziram um aumento nos níveis de ERO intracelulares nas culturas primarias, representativo de um efeito dual. Globalmente, microreatores demonstraram a capacidade de proteção antioxidante às células, oferecendo uma alternativa aos habituais agentes terapêuticos e representando um suporte enzimático para as células biológicas. Palavras-chave: stress oxidativo; mimetização celular; nanoflores de oxido de manganês; microreator.
ABSTRACT: The lack of antioxidant defences and high oxygen consumption rates render the brain vulnerable to oxidative stress. While most treatments target the scavenging of reactive oxygen species (ROS), cell mimicry does so by offering a long-term antioxidant support to protect the brain cell population from oxidative damage. Layer-by-layer microreactor assembling technique allows the development of personalized therapeutic particles, incorporating various active principles into targeting pertinent issues. For instance, catalytic activity can be achieved by superoxide dismutase (SOD) or manganese oxide (Mn3O4) nanoflowers. Incorporation of liposome-encapsulated enzyme SOD (LSOD) and/or nanoflowers in microreactors allows drawing a line between natural and artificial catalytic entities in cell mimicry. Thus, this work aimed to expand the use of microreactors to support neuroblastoma cells and mixed primary cultures against H2O2- and lipopolysaccharide (LPS) both physically and enzymatically. Microreactors were assembled with a polystyrene core, following by the deposition of polydopamine and poly-L-lysine precursor layers before immobilizing only nanoflowers or nanoflowers+LSOD as intermediate layers. Synthesized nanoflowers and microreactors showed both SOD and catalase activity, while LSOD retained low activity that was abolished by microreactor assembly, and therefore considered redundant for posterior use. While nanoflowers showed significant toxicity at low concentrations when incubated with cells, microreactors with integrated nanoflowers caused an inhibition of cell proliferation and only minor toxicity at high concentrations. Importantly, cells in the presence of the microreactors showed higher viability when subjected to H2O2, illustrating their capacity to rescue cells from oxidative stress induced death. Primary cultures showed consistence with the previous toxicity results but also a rise in intracellular ROS, reflective of possible underlying nanoflower effect. Taken together, microreactors with dual catalytic activity are a cell mimicry approach that can assist their mammalian counterpart to survive changes in their environment.

Yang, Kar Lai Alice.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references.
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts also in Chinese.

碩士
國立清華大學
材料科學工程學系
105
In the research field of piezo-catalytic material, the primary way of degradation process is mixing powder materials with dye solution directly. The color variation of dye solution is easy to be observed. In our previous work, MoS2 (Molybdenum disulfide) nanoflowers have highly piezo-catalytic properties. However, the greatly specific surface area of MoS2 nanoflowers results in the significant adsorption effect, which will hinder the analysis of degradation. In this study, we reported a new way of degradation, we mixed MoS2 nanoflowers with Di water and then ultrasonically vibrated for a period of time. Finally, we used centrifuge to separate the powder and solution, which was confirmed by simple measurement that over 99 % of the powder was removed. There would be a little single- and few- layered MoS2 nanoflowers remained in the solution and we found that the solution was catalytic. The catalytic properties of as-prepared solution were found to be proportional to the amount of MoS2 nanoflowers we added. The catalytic activity of the solution for decomposing Rhodamine B (RhB) solution could reach 80 % when 250 mg of the MoS2 nanoflowers was added. We could ignore the adsorption effect because of the 99 % removal of the powder. Therefore, OH radicals degradation mechanism could be regarded as the primary mechanism. The florescent spectra indicated the concentration of OH radicals in our as-prepared solution increases with the increasing amount of the MoS2 nanoflowers we added. The lifetime of OH radical in our as-prepared solution is up to five hours according to our observation. Our team thought that it is because of the F-center defects, which contributed to the amazingly long lifetime of OH radical.

碩士
國立中山大學
電機工程學系研究所
107
In this thesis, silicon substrate was etched into the inverted-pyramid morphology. Hydrothermal synthesized zinc oxide (ZnO) nanoflowers were spin-coated on the sidewalls of the silicon groove. The fabricated device is applied to ultraviolet (UV) detection. Both etched silicon and nanoflowers can enhance the surface-to-volume ratio of the device significantly. Therefore, the response of the device to UV can be improved. Structural and optical characteristics of ZnO nanoflowers were measured by means of X-ray diffraction, field-emission scanning electron microscopy, and photoluminescence. Based on the observation of SEM, different etching times lead to multiple substrate surface structures. The substrate etched for 10 min has the largest surface-to-volume ratio and causes the highest response to UV. Moreover, the device of etched substrate spin-coated with ZnO nanoflowers operated at 5 V reverse bias has the sensitivity of 128 % to short-wavelength UV (254 nm). Its response and recovery times are 24 and 60 s, respectively. Compared to planar devices (sputtered thin-film and unetched silicon substrate), the sensitivity of the device is highly enhanced.

Increasing energy demands as well as the depletion of traditional energy sources has led to the need for the development and improvement of energy conversion and storage technologies. Concerns regarding climate change and environmental awareness has also created increased support for renewable energy and clean technology research. One technology of interest is the photocatalyst, which is a material that is able to use natural light irradiation to create electrical currents or drive useful chemical reactions. For this purpose, a strong photocatalytic material has the following properties: i) strong absorbance over a wide solar radiation spectrum; ii) high surface area for adsorbance of target species; iii) high electron efficiency characteristics such as high conductivity, long charge-carrier lifetimes, and direct pathways for electron transport; and iv) good chemical stability. All of these requirements serve to maximize the efficiency and overall output of the device, and are a means of overcoming the performance hurdle required for the commercialization of various energy conversion technologies. Unfortunately, current photocatalytic materials suffer from small absorbance windows and high recombination rates which greatly reduce the conversion efficiency of the catalyst. Titanium dioxide (TiO2), the most well-known and widely used photocatalyst, can only absorb light within the ultraviolet (UV) range – which accounts for only a small fraction of the entire solar spectrum. For this reason, the majority of recent research has been directed toward producing photocatalysts that are able to absorb light within the visible and infrared range in order to maximize the amount of light absorbed in the solar spectrum. Other research is also being conducted to increase electrical conductivity and charge-carrier separation to further increase conversion efficiency. It is hoped that these two major problems surrounding photocatalysis can be solved by using novel functional nanomaterials. Nanomaterials can be synthesized using three main techniques: crystal structuring, doping, and heterostructuring. By controlling the structure of the crystal, materials of different phase, morphology, and exposed crystal facets can be synthesized. These are important for controlling the electronic properties and surface reactivity of the photocatalyst. Doping is the act of introducing impurities into a material in order to modify its band structure and create a red shift in light absorption. Lastly, heterostructuring is a method used to combine different photocatalysts or introduce co-catalysts in order to widen the range of absorption, encourage charge separation, or both. Many novel photocatalytic materials have been synthesized using these techniques. However, the next-generation photocatalytic material has remained elusive due to the high cost of production and complexity of synthesis. This thesis proposes a novel photocatalytic material that can be used in photocatalyzed waste-water remediation. Graphene-wrapped hierarchical TiO2 nanoflowers (G-TiO2) are synthesized using a facile synthesis method. TiO2 is a material of particular interest due to its chemical and photo-corrosion stability, high redox potential, strong electronic properties, and relative non-toxicity. Hierarchical structures are highly desired because they are able to achieve both high surface area and high conductivities. Graphene hybridization is a popular method for creating composites with highly conductive networks and highly adsorptive surfaces. To the best of my knowledge, the hybridization of graphene on hierarchical TiO2 structures without pre-functionalization of TiO2 has not yet been demonstrated in literature. Therefore, it is proposed that the use of such a material would greatly simplify the synthesis process and enhance the overall photocatalytic performance of TiO2 over that of commercial TiO2 photocatalysts. In the first study, hierarchical TiO2 nanoflowers are synthesized using a solvothermal reaction. It is then shown that under UV irradiation, the hierarchical TiO2 material is able to outperform commercial TiO2 material in the photodegradation of methylene blue (MB). Further characterization shows that this improvement is explained by a higher electrical conductivity, and exists in spite of having a lower specific surface area compared to the commercial material. In the second study, G-TiO2 is synthesized by mixing hierarchical TiO2 nanoflowers with graphene oxide (GO) and reducing GO in a hydrothermal reaction. Photocatalytic tests show that this hybridization further improves the performance of the hierarchical TiO2. Further studies reveal that an optimal graphene loading of 5 wt% is desired in order to achieve the higher rate of MB decomposition, and greatly outperforms P25 in this task. Characterization shows that G-TiO2 composites have increased specific surface area and electrical conductivity compared to the hierarchical TiO2 nanoflower. It is believed that this work will provide a simple and efficient avenue for synthesizing graphene–TiO2 composites with greatly improved photocatalytic activity. This work may also find use in other photocatalytic applications such as chemical deconstruction and manufacturing, hydrogen production, solar cells, and solar enhanced fuel cells.

碩士
國立中興大學
光電工程研究所
102
This study uses a hydrothermal method to fabricate nanoflower-like ZnO nanorods on patterned zinc-oxide (ZnO) seed layer arrays by lift-off technique. The structural properties of the ZnO seed layer and the growth mechanism and optical properties of the ZnO nanorods were explored under various process parameters including the thickness of the aluminum sacrificial layer, growth time of ZnO nanorods, and the concentration of the zinc acetate solution. As to effects of the sacrificial layer thickness, the 120 nm-thick aluminum sacrificial layer of 120nm had the shortest etching time and etching rate. XRD analysis found that the ZnO seed layer after lift-off was wurtzite structure and had a poor (002) orientation. SEM and EDS analyses showed that the longer etching time resulted from the thicker sacrificial layer and caused more impurities (aluminum) formed on the seed layer, thus hindering the growth of nanorods. As to effects of the growth time of nanorods, XRD results showed five peaks of the ZnO nanorods increased as the time increased, indicating that the nanorods did not grow perfectly perpendicular to the substrate. SEM and FIB analyses found that the length, width, aspect ratio and total surface area of the nanorods all increased with the growth time. Moreover, the transferred seed layer in 120nm had the highest efficiency of growth. In PL analysis, the intensity of UV light increased with the increasing of the time, and the intensity of green light became weaker as the defects reduced. The zinc defects would result in oxygen defects with the growth of time. As to effects of the concentration of the zinc acetate solution, it was also found that the peaks increased as the concentration of zinc acetate solution increased. The growth rate of the diameter of nanorods significantly increased with the increase of concentration, and it also led to the decrease of the aspect ratio and nanorods density. In PL analysis, the highest intensity of the UV peak was found from the sample with 0.02 M concentration, and the defects decreased with the increase of concentration.