Complement system includes a conglomeration of a set of soluble factors and membrane anchored receptors, which has been designed to recognise and clear non self (pathogens) and altered self (apoptotic cells, necrotic cells and transformed cells). In a general theme, the recognition subcomponents bind to target, which is followed by limited proteolytic cleavage of downstream complement components. Three pathways namely classical, alternative and lectin converge on the generation of C3 convertase. The alternative pathway is activated by spontaneous cleavage of C3, generating C3a, an anaphylatoxin, and C3b, which binds to the surface of pathogens. A C3 convertase is formed, which has a half-life of about 90 seconds, is stabilised by properdin, and in an amplification loop a C5 convertase is formed leading to lytic pathway and cell lysis. This puts properdin at the heart of up regulator of alternative pathway. Properdin is structurally organised into seven thrombospondin repeats (TSR), whose functions have been delineated via deletion mutagenesis studies. In the chapter 3, we have expressed TSR4 and TSR5 in tandem in E. coli and shown that the two-module recombinant protein binds to C3b, sulfatides, and glycosaminoglycans similarly to native properdin. The recombinant module also seems to be an efficient inhibitor of properdin’s ability to stabilise C3bBb complex, thus offering a therapeutic possibility to dampen alternative pathway. Although properdin’s definite role in perpetuating the alternative pathway is well established, its structural organisation also appears to suggest its potential as an independent innate immune soluble factor that would not require engagement with complement system. In chapter 4, we report the ability of properdin to interact with mycobacterium (BCG) via TSR4+5 module, down regulate the microbial uptake by macrophages, and up regulate pro-inflammatory cytokine response via enhancing anti-mycobacterial TNF-α production. In chapter 5, we demonstrate that properdin as well as TSR4+5 interacts directly with a range of influenza A virus strains leading to inhibition of infection and dampening of pro-inflammatory response. The ability of properdin to interact with non-self is further reaffirmed by its ability to interact with nanoparticles and modulate subsequent immune cell response as presented under discussion chapter. Thus, this thesis reports a set of novel observations highlighting non-complement properties of properdin, which may be crucial in host pathogen interaction.

Automated tracking of cells across timelapse microscopy image sequences typically employs complex segmentation routines and/or bio-staining of the tracking objective. Often accurate identification of a cell's morphology is not of interest and the accurate segmentation of cells in pursuit of non-morphological parameters is complex and time consuming. This thesis explores the potential of internalized quantum dot nanoparticles as alternative, bio- and photo-stable optical markers for tracking the motions of cells through time. CdTe/ZnS core-shell quantum dots act as nodes in moving light display networks within A549, epithelial, lung cancer cells over a 40 hour time period. These quantum dot fluorescence sources are identified and interpreted using simplistic algorithms to find consistent, non-subjective centroids that represent cell centre locations. The presented tracking protocols yield an approximate 91% success rate over 24 hours and 78% over the full 40 hours. The nanoparticle moving light displays also provide simultaneous collection of cell motility data, resolution of mitotic traversal dynamics and identification of familial relationships enabling the construction of multi-parameter lineage trees. This principle is then developed further through inclusion of 3 different coloured quantum dots to create cell specific colour barcodes and reduce the number of time points necessary to successfully track cells through time. The tracking software and identification of parameters without detailed morphological knowledge is also demonstrated through automated extraction of DOX accumulation profiles and Cobalt agglomeration accruement statistics from two separate toxicology assays without the need for cell segmentation.

Les nanoparticules (NPs) concentrent beaucoup d’espoir en nanomédecine, en particulier les nanoparticules magnétiques de silice mésoporeuse (M-MSN) qui pourraient permettre des avancées en théranostic. Néanmoins l’innocuité de ces NPs recouvertes de décorations leur conférant des propriétés spécifiques, doit être démontrée afin d’éviter des effets néfastes sur les tissus sains, notamment sur le foie, l’organe de transformation des xénobiotiques. L’objectif de cette thèse était donc d’évaluer la toxicité potentielle de M-MSN soit natives, soit recouvertes de polyéthylène glycol (PEG), soit entourées d’une bicouche lipidique de 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Pour ce faire un modèle de cellules humaines hépatiques (HepaRG) a été choisi pour effectuer des tests de toxicité in vitro et pour élucider le mode d’action intracellulaire de ces différentes NPs.Les caractéristiques physico-chimiques des M-MSNs natives et décorées ont été mesurées par différentes techniques comme la diffusion dynamique de la lumière (DLS), la microscopie électronique à transmission (TEM) et la microscopie à force atomique (AFM). La toxicité des NPs a été évaluée tout d’abord par des tests de viabilité et par impédance cellulaire en temps réel (xCELLigence).L’étude des profils d’expression génique sur des oligo microarrays à très haute densité (8x60k sondes, Agilent) a ensuite permis d’évaluer, de façon dose- et temps-dépendante, la toxicité de ces NPs. De plus l’utilisation d’une méthodologie originale d’analyse comparative de données massives nous a permis de mettre en évidence les mécanismes moléculaires déclenchés par les NPs dans les hépatocytes. Nous avons déterminé des doses n’induisant aucune toxicité ou une légère toxicité transitoire après 24h, soit une valeur seuil de biocompatibilité avec les cellules HepaRG. Nous avons également montré par TEM le ralentissement de l’internalisation des NPs lorsqu’elles sont PEGylées ainsi que leurs effets transcriptomiques différés par rapport aux NPs natives et lipidiques. Néanmoins, une dose de 80 µg/cm² de M-MSNs, natives ou décorées, déclenche l’enchaînement des évènements de l’AOP (Adverse Outcome Pathway) de la cholestase hépatique. Ce résultat démontre que cette méthodologie est adaptée à la toxicologie prédictive par analyse des réponses biologiques cellulaires après exposition à des substances exogènes.Par ailleurs, les NPs ont tendance à se recouvrir de protéines (corona) en présence de sérum humain. L’analyse par impédance cellulaire montre que des M-MSNs entourées d’une corona de protéines sériques humaines ou bovines ne provoquent pas la même toxicité sur des cellules humaines. Ce résultat pose la problématique d'une potentielle surestimation de la toxicité des nanoparticules lors d’essais in vitro, utilisant classiquement du sérum de veau dans les milieux de cultures.Nous avons entrepris l’étude de la dynamique de la corona (entre 30s et 7 jours) par spectrométrie de masse en tandem. Cette analyse a mis en lumière trois types de comportements protéiques. Le premier cluster contient des protéines abondantes qui se désorbent au cours du temps, le second cluster est composé de protéines qui s’enrichissent progressivement et issues de mêmes familles protéiques comme les apolipoprotéines, et le troisième cluster contient des protéines à enrichissement tardif dans la corona, attirées par leur affinité pour des protéines déjà présentes. Un réseau dynamique d’interactions protéines-protéines, ou intéractome, a pu être cartographié au sein de la corona. Ces travaux posent les bases d’un possible contrôle des protéines de la corona afin de conférer aux nanovecteurs des propriétés de furtivité leur permettant d’atteindre des organes cibles sans être opsonisés. Les techniques utilisées au cours de ce travail, basées sur les analyses de quantités massives de données biologiques, pourraient faire partie de futurs standards d’évaluation de la nanosécurité. / Nanoparticles (NPs) capable of transporting and releasing therapeutic agents to target tissues constitute one of the most exciting areas in nanomedicine, especially magnetic mesoporous silica nanoparticles (M-MSN). M-MSNs may be addressed to tumors thanks to their magnetism and can act as drug carriers thanks to their high specific surface area. Nevertheless, the safety of these NPs with decorations, conferring them specific properties, must be assessed in order to avoid harmful effects on healthy tissues, in particular on the liver, the organ of xenobiotics metabolism.The goal of this thesis was therefore to evaluate the potential toxicity of M-MSN either pristine, or coated with polyethylene glycol (PEG), or surrounded by a lipid bilayer of 1,2-dimyristoyl-sn-glycero-3- Phosphocholine (DMPC). To this end, the human hepatic cell model HepaRG was chosen to realize in vitro toxicity testing and to elucidate the intracellular mode of action of these various NPs.The physico-chemical properties of pristine and covered M-MSNs were measured using different techniques such as dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). NPs toxicity was first evaluated by viability testing and real-time cell impedance analysis (xCELLigence).Gene expression profiles were then performed through very high density oligo microarrays (8x60k, Agilent) to evaluate, in a dose- and time-dependent manner, the toxicity of these NPs. In addition, the use of an original methodology for comparative analysis of large biological data allowed us to demonstrate the molecular mechanisms triggered by the NPs in the hepatocytes. We were able to determine the dose not triggering any toxicity as well as the dose inducing a slight transient toxicity after 24h. We thus defined this latter value as a threshold of biocompatibility with HepaRG cells. We also showed by TEM a slower uptake of PEGylated NPs by cells as well as their delayed effects on the transcriptome compared to the pristine and DMPC NPs. Nevertheless, a dose of 80 μg/cm² of pristine or covered M-MSNs triggers the chain of events of the hepatic cholestasis AOP (Adverse Outcome Pathway). This result demonstrates that this methodology is suitable for predictive toxicology by analysis of cellular biological responses after exposure to exogenous substances.Furthermore, NPs tend to be covered with proteins in the presence of serum (corona). Cell impedance analysis shows that M-MSNs surrounded by human or bovine serum proteins coronas do not trigger the same toxicity on human cells. This result raises the problem of a potential overestimation of NPs toxicity to human cells in in vitro testing by using fetal bovine serum in culture media.We undertook a dynamic analysis (between 30 s and 7 days) of the corona formation by tandem mass spectrometry has highlighted three groups of protein with distinct behaviors. The first cluster contains some abundant proteins that desorb over time, the second cluster comprises some protein families such as apolipoproteins, and the third cluster contains late enrichment proteins attracted by other proteins already present in the corona. A dynamic network of protein-protein interactions inside the corona, namely the interactome, was built from the data. This work opens the way to a possible control of the corona in order to provide the nanocarriers with stealth properties allowing them to reach target organs without being opsonized.These techniques used during this thesis and based on analyses of biological big data might be part of the future standards on nanosafety evaluation.

This thesis provides several nanomaterial systems that can be used as contrast agents in magnetic resonance imaging (MRI) and for optical fluorescence imaging. Nanoparticle systems described in this thesis fall under three categories: (a) graphene oxide-nanoparticle composites for MRI contrast agent application, (b) core-shell nanoparticles for MRI contrast agent application and (c) nanoparticle systems for both MRI and optical fluorescence imaging. In the case of graphene oxide based nano-composites, the following observations were made: (i) in the case of graphene oxide-Fe3O4 nanoparticle composite, it was observed that high extent of oxidation of the graphene oxide and large spacing between the graphene oxide sheets containing Fe3O4 nanoparticles provides the optimum structure for yielding a very high transverse proton relaxivity value, (ii) in the case of graphene oxide-Gd2O3 nanoparticle composite, it was observed that this composite exhibits high value for both longitudinal and transverse relaxivity values making it a potential materials for multi-contrast study of pathologies with a single agent, (iii) in the case of graphene oxide-CoFe2O4 nanoparticle composites, it was observed that an increase in the reflux time of the reaction mixture containing this composite led to appreciable variations in the proton relaxivity values. Transverse relaxivity value of the water protons increased monotonically with increase in the reflux time. Whereas, the longitudinal relaxivity value initially increased and then decreased with increase in the reflux time. In the case of coreshell nanoparticles for MRI contrast agent application two different core-shell systems were investigated. They are MnFe2O3-Fe3O4 core-shell nanoparticles and CoFe2O4-MnFe2O4 coreshell nanoparticles. Investigations of both the core-shell nanoparticle systems revealed that the proton relaxivity value obtained in the dispersion of the core-shell nanoparticles was considerably greater than the proton relaxivity value obtained in the presence of single phase nanoparticles of the core and shell phases. Very high value of transverse relaxivity in the case core-shell nanoparticles was due to the large magnetic inhomogeneity created by the core-shell nanoparticles in the water medium surrounding it. In the case of nanoparticle systems for both MRI and optical fluorescence imaging, two different systems were investigated. They were CoFe2O4-ZnO core-shell nanoparticles and Gd doped ZnS nanoparticles [Zn1-xGdxS, x= 0.1, 0.2 and 0.3] formed on graphene oxide sheets or coated with chitosan. In the case of CoFe2O4-ZnO core-shell nanoparticles it was observed that fluorescent CoFe2O4-ZnO core-shell nanoparticles with the unique geometry in which CoFe2O4 ferrite nanoparticles agglomerates were present within larger sized hollow ZnO capsules yields very high value of transverse proton relaxivity when compared to the proton relaxivity value exhibited by the individual CoFe2O4-ZnO coreshell nanoparticles. In the case of Gd doped ZnS nanoparticles, two different systems were synthesized and the values of the longitudinal and transverse proton relaxivity obtained were compared. These systems were (i) graphene oxide- Zn1-xGdxS (x= 0.1, 0.2 and 0.3) nanoparticle composites and (ii) chitosan coated Zn1-xGdxS (x= 0.1, 0.2 and 0.3) nanoparticles. It was observed that Gd doped ZnS nanoparticles in both cases exhibit both longitudinal and transverse relaxivity values. The relaxivity values showed a clear dependence on the composition of the nanoparticles and the nanoparticle environment (presence and absence of graphene oxide). It was also observed that Gd doped ZnS nanoparticle can be used for florescence imaging.

Master of Science / Department of Physics / Christopher M. Sorensen / An easier, cheaper and scalable method to obtain silver nanoparticles, AgNPs, directly from the bulk material has been obtained. Two different solvents were tried, water and ethylene glycol, the coating agent was polyvinylpyrrolidone, PVP, and two different silver sizes were used, micron size powder and silver shots, millimeter size. It was seen that changing the size of bulk silver, the temperature of reaction, the amount of oxygen, the concentration of PVP and its molecular weight all had an important influence in the synthesis of nanoparticles. Different morphologies could be obtained when these parameters were adjusted ranging from spheres to triangles and hexagons. A complex mechanism is proposed: during the first step, bulk silver is oxidized by oxygen in solution, forming a thin layer of oxidized silver on the surface. Then, PVP acts as a reducing agent at the oxidized surface, where silver becomes Ag⁰ again. At the same time that PVP reduces the oxidized silver back to metallic silver; it coordinates with the silver atoms acting as a protecting agent. That coordination between PVP and silver pulls out the atoms and produces a detachment of silver atoms from the bulk surface. These silver-PVP complexes in solution later combine to form silver nanospheres and evolve to rods first and then triangles and hexagon with longer reaction time.

abstract: Structural details of phosphonic acid functionalized nanomaterials and protic ionic liquids (PILs) were characterized using nuclear magnetic resonance (NMR) spectroscopy. It is well known that ligands play a critical role in the synthesis and properties of nanomaterials. Therefore, elucidating the details of ligand-surface and ligand-ligand interactions is crucial to understanding nanomaterial systems more completely. In an effort to further the understanding of ligand-surface interactions, a combination of multi-nuclear (1H, 29Si, 31P) and multi-dimensional solid-state NMR techniques were utilized to characterize the phosphonic acid functionalization of fumed silica nanoparticles using methyl phosphonic acid (MPA) and phenyl phosphonic acid (PPA). Quantitative 31P MAS solid-state NMR measurements indicate that ligands favor a monodentate binding mode. Furthermore, 1H-1H single quantum-double quantum (SQ-DQ) back-to-back (BABA) 2D NMR spectra of silica functionalized with MPA and PPA indicate that the MPA and PPA are within 4.2±0.2 Å on the surface of the nanomaterial. The ligand capping of phosphonic acid (PA) functionalized CdSe/ZnS core-shell quantum dots (QDs) was investigated with a combination of ligand exchange, solution and solid-state 31P NMR spectroscopy. In order to quantify the ligand populations on the surface of the QDs, ligand exchange facilitated by PPA resulted in the displacement of the PAs, and allowed for quantification of the free ligands using 31P liquid state NMR. In addition to characterizing nanomaterials, the ionicity and transport properties of a series of diethylmethylamine (DEMA) based protic ionic liquids (PILs) were characterized, principally utilizing NMR. Gas phase proton affinity was shown to be a better predictor for the extent of proton transfer, and in turn the ionicity of the PIL, than using ∆pKa. Furthermore, pulsed field gradient (PFG) NMR was used to determine that the exchangeable proton diffuses with the cation or the anion based on the strength of the acid used to generate the PILs. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2015

Orientador: Juliane Maria Guerreiro Tanomaru / Co-orientador: / Banca: Gisele Faria / Banca: Idomeo Bonetti Filho / Banca: Evandro Watanabe / Resumo: Enterococcus faecalis apresenta elevada resistência às medicações intracanal. O emprego de substâncias nanoparticuladas e a associação à clorexidina podem interferir na efetividade da medicação. O objetivo deste estudo foi avaliar pH e atividade antibacteriana de pastas à base de hidróxido de cálcio (HC) e óxido de zinco (ZnO) microparticulados (micro) ou nanoparticulados (nano) associados ou não à clorexidina 0,4% frente ao Enterococcus faecalis. Foram analisadas as pastas: HC/ZnO micro; HC/ZnO nano; HC/ZnO micro + Clorexidina a 0,4%; HC/ZnO nano + Clorexidina a 0,4%. O polietilenoglicol 400 foi usado como veículo. A atividade antibacteriana frente ao Enterococcus faecalis foi avaliada por três estudos in vitro: Estudo de Difusão em Ágar, Teste de Contato Direto em Células Planctônicas e por meio de Biofilme Induzido em Canais Radiculares de Dentes Humanos. A análise do pH foi determinada por meio da Difusão em Dentes Bovinos e por Dissociação em Tubos de Polietileno. Os resultados dos estudos obtidos foram submetidos aos testes estatísticos ANOVA e Tukey ou Kruskall-Wallis e Dunn, com nível de significância de 5%. Os resultados dos testes Difusão em Ágar mostraram que a medicação HC/ZnO nano e pastas com clorexidina 0,4% foram mais efetivas. No Contato Direto as pastas com clorexidina mostraram maior atuação após 30 segundos e todas eliminaram Enterococcus faecalis após 1 minuto. O teste de Difusão em Dentina Bovina mostrou maior aumento de pH para as medicações nanoparticuladas nos períodos de 1 e 7 dias (p<0,05). Todas as pastas promoveram aumento do pH de forma similar (p>0,05) no Teste com Tubos de Polietileno. A avaliação em canais radiculares demonstrou que as pastas foram efetivas na coleta após a sua remoção, mas na coleta final as medicações com clorexidina apresentaram maior redução bacteriana (p<0,05). Conclui-se que ...(Resumo completo clicar acesso eletrônico abaixo) / Abstract: Enterococcus faecalis presents high resistance to intracanal medications. The use of nanoparticulate substances and the association with chlorhexidine may interfere with the effectiveness of the medication. The aim of this study was to evaluate pH and antibacterial activity of medications based microparticulate (micro) or nanoparticles (nano) calcium hydroxide (CH) and zinc oxide (ZnO) associated or without chlorhexidine 0.4% against Enterococcus faecalis. Medications were analyzed: HC / ZnO micro; HC / ZnO nano; HC / ZnO micro + Chlorhexidine 0.4%; HC / ZnO nano + Chlorhexidine 0.4%. Polyethylene glycol 400 was used as vehicle. The antibacterial activity against E. faecalis was evaluated by three in vitro studies: Study of Diffusion in Agar, Testing of Direct Contact in planktonic cells and through induced biofilm in root canals of human teeth. The analysis of pH was determined using bovine teeth of diffusion and dissociation of polyethylene tubes. The results of studies obtained were submitted to ANOVA and Tukey or Kruskal-Wallis and Dunn, with a significance level of 5%. The results of the agar diffusion test showed that the HC / ZnO nano and with 0.4% chlorhexidine medication were more effective. In Direct Contact medication with chlorhexidine showed increased activity after 30 seconds are all eliminated Enterococcus faecalis after 1 minute. The diffusion test for bovine dentin showed higher pH increase for nanoparticulate medication in periods 1 and 7 days (p <0.05). All medications pH increase promoted similarly (p> 0.05) in test tubes of polyethylene. The evaluation showed that in root canals medication so effective in collecting after their removal, but the final collection medications with chlorhexidine showed higher bacterial reduction (p <0.05). It is concluded that the nanoparticles of calcium hydroxide and zinc oxide promote greater dentinal diffusion and high pH in the...(Complete abstract electronic acess below) / Doutor

Nanomateriais, incluindo as nanopartículas e nanotubos, tem sido extensivamente utilizados em diversas aplicações tecnológicas, devido principalmente às suas interessantes propriedades, advindas da alta relação área/volume. Para a efetiva aplicação destes materiais em dispositivos nanotecnológicos, no entanto, é crucial o desenvolvimento de sistemas altamente estáveis, que mantenham suas propriedades por longos períodos. Neste trabalho foi proposta uma rota sintética para a preparação de nanopartículas de ouro na presença de polieletrólitos e tióis numa só fase, juntamente com um estudo sistemático da estabilidade dos sistemas produzidos. Os espectros de UV-vis obtidos demonstraram a formação de nanopartículas de ouro, com banda plasmônica característica. As nanopartículas foram também visualizadas por imagens de microscopia de Transmissão. Análise de espectroscopia na região do infravermelho (FTIR) mostraram as ligações químicas que ocorrem entre os materiais constituintes dos sistemas híbridos de AuNPs. O estudo de estabilidade das AuNps foi realizado com medidas de espalhamento de luz dinâmico (DLS) bem como por medidas de UV-vis, o que permitiu a obtenção do tipo de solução e condições mais estáveis. Através de análise estatística, por meio da análise de componentes principais (PCA), foi possível verificar quais fatores influenciam de forma significativa a estabilidade das diferentes soluções preparadas. / The use of nanomaterials - including nanoparticles and nanotubes - for technological applications has received tremendous attention in the last few years, mainly due to their unique, size-dependent properties. The proper application of such nanomaterials in technological devices, however, has been limited by parameters such as their physical or chemical stability. In this Master´s dissertation, we introduce a single step synthetic route for preparation of gold nanoparticles in the presence of polyelectrolytes and thiols, with emphasis on the stability of the nanomaterials under different storage conditions. Four different hybrid nanoparticles had been investigated, containing either PAH or PVA as the polymeric phase, in the presence of 3-AMP or 11-AMP thiols, respectively. After synthesis, the formation of the Au nanoparticles (AuNPs) was evidenced by UV-vis spectroscopy, upon appearance of a characteristic plasmonic band centered at ca. 510 or 540 nm, depending on the stabilizing agents used. The AuNPs were also investigated via TEM images. FTIR analyses evidenced that electrostatic interactions occurred between the thiols and the polyelectrolytes, within the hybrid nanoparticles structure. The stability of the four different systems was detailed investigated using UV-Vis spectroscopy, dynamic light scattering (DLS), and visual analyses. The data pointed to the higher stability presented by the AuNps stabilized with PAH in the presence of 3-AMP (PAH/3-AMP AuNPs). In contrast, the AuNPs stabilized with PVA exhibited the lowest stability. This feature was corroborated by statistical analysis, using principal component analysis (PCA), through which was possible to identify the main factor affecting AuNPs stability.

Made available in DSpace on 2014-06-11T19:23:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-02Bitstream added on 2014-06-13T19:08:53Z : No. of bitstreams: 1 silva_dr_me_araiq.pdf: 984256 bytes, checksum: bcc952300b822c0cddcc1c2d5f5eec53 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A biolixiviação (lixiviação bacteriana) é uma alternativa para a extração de metais presentes em sulfetos minerais empregando microorganismos. Dentre as principais vantagens da biohidrometalurgia em relação aos métodos convencionais podem ser destacadas a não-emissão de SO2 para a atmosfera, pequeno gasto com insumos, pois são produzidos pelos próprios microorganismos, baixa demanda energética e o tratamento de minérios contendo metais em baixo teor. Uma das espécies envolvidas na biolixiviação de sulfetos minerais mais estudadas é Acidithiobacillus ferrooxidans. Essa bactéria é gram negativa, aeróbia, acidófila, mesófila e obtém energia através da oxidação de íons Fe2+ e compostos reduzidos de enxofre. A calcopirita é a principal fonte de cobre presente na crosta terrestre. Uma das principais propriedades desse sulfeto é a sua alta refratariedade ao ataque químico e bacteriano, conseqüência da sua elevada energia de rede cristalina. Além disso, a formação de uma camada protetora, constituída basicamente por polissulfetos, sobre a sua superfície diminui a dissolução desse minério. Por isso, diversos grupos de pesquisa buscam alternativas para a resolução desses problemas visando elevar as extrações de cobre a partir desse sulfeto. Com esse objetivo, o presente trabalho estudou o efeito da adição de nanopartículas, polares e apolares, na biolixiviação da calcopirita por A. ferrooxidans LR. O único estudo relacionado à lixiviação envolvendo nanopartículas demonstrou que a adição de nanosílica elevou as taxas de dissolução da calcopirita mediante utilização de agentes oxidantes, meio reacional ácido e temperatura moderada. Para avaliar o efeito da adição de nanopartículas no crescimento bacteriano, foi monitorada a concentração de íons Fe2+ presentes em sistemas contendo A. ferrooxidans... / Bioleaching is an alternative for metal extraction from mineral sulfides using microorganisms. The main advantages of the biotechnological processes in comparison with usual methods of metal extraction are the non-emission of SO2 to atmosphere, lower inputs cost, as they are produced by the microorganisms themselves, lesser energy requirements and treatment of low-grade ores. One of the most studied microbes involved in the bioleaching of mineral sulfides is Acidithiobacillus ferrooxidans. This bacterium is Gram-negative, aerobic, acidophilic, mesophilic and oxidizes Fe2+ ions and reduced forms of sulfur to obtain energy. Chalcopyrite is the main copper source present in the world. One of its main properties is the high resistance to the chemical and bacterial attacks, result of its great crystal lattice energy. Also, the formation of a protective layer, mainly constituted by polysulfides, over its surface reduces the dissolution of that ore. For those reasons, several research groups throughout the world are investigating alternatives to solve these problems and promote the higher copper extraction from this sulfide. This work studied the effect of adding nanoparticles, polar and non-polar, in the bioleaching of chalcopyrite by A. ferrooxidans LR. The only study related to leaching involving nanoparticles, published in 2005, demonstrated that the addition of nano-sized silica raised the dissolution rates of chalcopyrite when using oxidizing agents, acidic medium and moderate temperature. To evaluate the effect of adding nanoparticles in bacteria growth, it was monitorated the Fe2+ ions concentration present in flasks that contained A. ferrooxidans LR and different concentrations of nanoparticles. Thus, it was observed that high amounts of nanoparticles (> 2.5% m/v) affected the bacteria growth. Shake flasks... (Complete abstract click electronic access below)

Upconversion nanoparticles (UCNPs) have been utilized for biological applications. Unlike conventional linear excitation molecules, UCNPs are excited by 980nm and emit photon in visible and near infrared region. The unique photophysical property offers superior penetration depth and lower photo-cytotoxicity. With the aid of various vectors such as target-specific peptides and photosensitizers, the UCNPs can precisely interact selectively with designated proteins (Cyclin D1 and Polo-like Kinase 1) and cancer cells so as to achieve theranostic effect. This thesis illustrated the upconversion mechanism and anti-cancer effect by UCNPs conjugated with peptides. Two research studies focus on Cyclin D1 or Polo-like kinase 1 (Plk1) specific peptides coated UCNPs function as key cell cycle inhibitors, in vitro imaging agent and in vivo tumor suppressor. Apart from inorganic nanomaterials, graphitic phase carbon nitride (g-C3N4) nanoparticles coupled with porphyrin moieties act as cancer directional photodynamic therapy agents was also described in the aspects of detailed photophysical measurements and in vitro theranostic studies.