Synthetic polymeric materials have gained significant use as biological materials (biomaterials) in biomedical and pharmaceutical applications. As a result, a demand for well-defined polymers with tunable properties has emerged. The synthetic versatility of polymeric biomaterials allows the opportunity to understand the structure-property relationship of materials and their cellular interactions. A novel class of polymeric biomaterials are conjugated polymers (CPs), which possess desirable physicochemical and excellent photophysical properties, including inherent fluorescence. The synthetic versatility of CPs allows easy modification of the conjugated backbone to tune emission and side chain structures to adjust biocompatibility through increased water solubility, controlled biodegradability, and incorporation of targeting units. The aim of this dissertation is to better understand conjugated polymer nanoparticle (CPN) structure and self-assembly in an aqueous environment, and how those structural features affect cellular interactions to establish a structure-function relationship. This work presents the fabrication of several different CPNs for cancer cell targeting and labelling, and differentiation of biologically important molecules. Core−shell nanoparticles were prepared using a semi-flexible cationic CPN complexed with hyaluronic acid (HA), a polyanion. The resulting CPNs exhibited high cancer cell specificity with low adsorption to normal cells, as a result of HA’s affinity towards overexpressed receptors on cancer cell surface. A systematic investigation on the aggregation properties of CPNs that vary by side chain and backbone structures in response to different biologically important anionic polysaccharides in a complex biological medium was conducted. Mitochondria-specific CPNs were fabricated from a semi-flexible CPN modified with the mitochondrial-targeting triphenylphosphonium (TPP) group. The subcellular localization and cellular toxicity were dependent on backbone flexibility, hydrophilicity, and molecular weight. Dual-targeting CPNs grafted with folic acid (FA) side chains and complexed with hyaluronic acid (HA) were fabricated for improved uptake and bioimaging of cancer cells. The work presented here shows how modifications to CPN backbone and side chain structures modulate their cellular interactions. The physicochemical and biophysical properties of CPNs affect biocompatibility and understanding those properties will lead to the development of novel CP-based biomaterials.

Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year. However, traditional treatments have proven insufficient for successful medical management of cancer due to the chemotherapeutics’ difficulty in achieving therapeutic concentrations at the target site, non-specific cytotoxicity to normal tissues, and limited systemic circulation lifetime. Although, a concerted effort has been placed in developing and successfully employing nanoparticle(NP)-based drug delivery vehicles successfully mitigate the physiochemical and pharmacological limitations of chemotherapeutics, work towards controlling the subcellular fate of the carrier, and ultimately its payload, has been limited. Because efficient therapeutic action requires drug delivery to specific organelles, the subcellular barrier remains critical obstacle to maximize the full potential of NP-based delivery vehicles. The aim of my dissertation work is to better understand how NP-delivery vehicles’ structural, chemical, and physical properties affect the internalization method and subcellular localization of the nanocarrier. In this work we explored how side-chain and backbone modifications affect the conjugated polymer nanoparticle (CPN) toxicity and subcellular localization. We discovered how subtle chemical modifications had profound consequences on the polymer’s accumulation inside the cell and cellular retention. We also examined how complexation of CPN with polysaccharides affects uptake efficiency and subcellular localization. This work also presents how changes to CPN backbone biodegradability can significantly affect the subcellular localization of the material. A series of triphenyl phosphonium-containing CPNs were synthesized and the effect of backbone modifications have on the cellular toxicity and intracellular fate of the material. A mitochondrial-specific polymer exhibiting time-dependent release is reported. Finally, we present a novel polymerization technique which allows for the controlled incorporation of electron-accepting benzothiadiazole units onto the polymer chain. This facilitates tuning CPN emission towards red emission. The work presented here, specifically, the effect that side-chain and structure, polysaccharide formulation and CPN degradability have on material’s uptake behavior, can help maximize the full potential of NP-based delivery vehicles for improved chemotherapeutic drug delivery.

Atualmente no Brasil mais da metade da população adulta tem excesso de peso e 21% estão obesos. A obesidade é uma doença que se encontra em evidente crescimento, sendo considerada a epidemia do século XXI. Como alternativa de tratamento e prevenção, o uso de ácidos graxos que possuem habilidade de induzir a expressão de genes com importante papel em modulações metabólicas e mitocondriais têm sido estudados. O ácido linoleico conjugado (CLA, 18:2) é da família ômega-6, descrito por sua propriedade antiobesidade relacionada à diminuição da adiposidade e ao aumento do metabolismo corporal. O óleo de peixe (OP) é uma mistura de ácidos graxos poli-insaturados eicosapentaenóico (EPA, 20:5) e docosahexaenóico (DHA, 22:6) da família ômega-3, conhecido por aumentar a sensibilidade à insulina, o colesterol-HDL, pelas suas propriedades antiinflamatórias e sua ação protetora sobre o sistema nervoso. O objetivo deste estudo foi verificar os efeitos da suplementação da dieta de camundongos C57BL6 com CLA em conjunto com OP durante 60 dias sobre aspectos bioquímicos, moleculares e fisiológicos do metabolismo mitocondrial e corporal. Verificamos que a suplementação da dieta com CLA e OP in vivo: aumenta o metabolismo corporal, efeito atribuído à ambos os óleos; prejudica o metabolismo da glicose circulante, proporcionado exclusivamente pelo CLA; reduz o nível de movimentação, proporcionado exclusivamente pelo OP. No fígado: aumenta a expressão de UCP2, a atividade de proteínas desacopladoras e a ?- oxidação, efeito atribuído à ambos os óleos; aumenta o número de mitocôndrias, proporcionado exclusivamente pelo OP. CLA aumenta a produção de espécies reativas de O2 (EROs) a qual é revertida pelo OP em conjunto. No músculo sóleo: aumenta a biogênese mitocondrial via PGC- 1? e a expressão de UCP2, proporcionados pelo OP. Por fim, no hipocampo: aumenta o número de mitocôndrias, estimulo dado por ambos os óleos; aumenta a atividade desacopladora e reduz a produção de EROs, proporcionados exclusivamente pelo CLA. Concluímos que na suplementação conjunta os efeitos do OP são predominantes nos metabolismos corporal, hepático e muscular, e na movimentação corporal, enquanto que o efeito predominante do CLA é a diminuição na sensibilidade à insulina. Já no cérebro, o OP potencializa os efeitos do CLA. / Currently in Brazil more than a half of adult population has overweight, and 21% are obese. This evident growing disease is considered the 21th century\'s epidemy. Some fatty acids have been considered an alternative treatment and prevention strategy for obesity due to their ability to stimulate gene expression with important role in cellular and mitochondrial metabolisms. Conjugated linoleic acid (CLA, 18:2) from omega-6 family, with anti-obesity properties related to diminution of adiposity and increments in body metabolism. The fish oil (FO) is a mixture of the poli-unsaturated fatty acids eicosapentaenoic (EPA, 20:5) and docosahexaenoic (DHA, 22:6) from omega-3 family, known for improving insulin sensibility and HDL-cholesterol, anti-inflammatory properties and protective action over the central nervous system. The objective of this study was to examine the effects of dietary supplementation of CLA in conjunction with FO during 60 days over biochemical, molecular and physiological aspects of mitochondrial and body metabolism in C57BL6 mice. Diet supplementation with CLA and FO in vivo: raise body metabolism, an effect attributed to both oils; affect glucose metabolism, exclusively proportionate by CLA; diminish the level of mice movement, exclusively proportionate by FO. In liver: increase UCP2 expression, uncoupling proteins activity and ?-oxidation, stimulated by both oils; increase mitochondrial density, exclusively proportionate by FO. CLA also raises the reactive oxygen species (ROS) production, which is reversed by FO in conjunction. In soleus muscle: increase mitochondrial biogenesis through PGC-1? and the UCP2 expression, exclusively proportionate by FO. Lastly, in hippocampus: increase mitochondrial density, stimulated by both oils; stimulate uncoupling activity and diminish ROS production, exclusively proportionate by CLA. In conclusion, in the dietary supplementation with CLA and FO in conjunction the FO effects are prevalent in metabolisms of body, liver and muscle, and in body movement, while the CLA effects are prevalent in decreasing insulin sensitivity. However in the brain, the FO potentiates the effects of CLA.

Recentemente tem sido observado grande avanço na área de fotovoltaicos orgânicos e híbridos. Esses dispositivos baseiam-se em diferenças de energia eletrônica nas interfaces dos componentes de uma heterojunção, onde as heterojunções dispersas obtidas via arranjos interpenetrantes com estes dois compostos, em dimensões sub-20-nm, permite coleção efetiva dos portadores de carga fotogerados, mesmo com pequeno comprimento de difusão do éxciton e baixa mobilidade dos portadores de carga. Desta maneira, o estudo e a modificação da interface entre as duas fases é essencial para melhorar a eficiência de conversão desses dispositivos. Este trabalho tem como objetivo investigar heterojunções de dióxido de titânio (TiO2)/poli(3-hexil tiofeno) (P3HT) como camadas ativas em dispositivos fotovoltaicos híbridos. Essas heterojunções são atraentes para fotovoltaicos híbridos por permitir a nanoestruturação do metalóxido antes da incorporação do polímero, levando à obtenção de elevada área interfacial e com a possibilidade de ajustar as propriedades interfaciais mantendo o caráter aceitador/doador desta heterojunção. Os filmes de TiO2 foram obtidos a partir de dispersões coloidais de nanopartículas de anatase, enquanto aqueles de P3HT foram obtidos a partir de sua solução de 1,2-diclorobenzeno. Como eletrodos foram utilizados o óxido de índio dopado com óxido de estanho (ITO) e ouro (Au). A caracterização elétrica e espectroscópica indicou que os parâmetros fotovoltaicos, bem como absorção e fotoluminescência, dependem da submissão dos dispositivos a tratamentos térmicos post-production, evidenciando que o aquecimento induz a mudanças conformacionais no polímero, alterando a interface óxido/polímero. A introdução de grupos carboxilato nas ramificações 3-hexil do P3HT permite melhor contato entre óxido/polímero, sendo favorecido por tratamento térmico. Mais ainda, a infiltração do polímero em filmes de TiO2 nanocristalino levou à obtenção de dispositivos fotovoltaicos de considerável estabilidade, apresentando atividade mesmo após 6 meses após a elaboração destes. Finalmente, neste trabalho também é proposta a utilização de um complexo a base de ftalocianina de zinco como modificador de interface do TiO2, cuja absorção estende a janela espectral do dispositivo até o vermelho e infravermelho próximo. Estudos de fenômenos de transporte, levando-se em conta a fotogeração de portadores e sua recombinação, foram realizados por medidas do espectro de fotocondução no dispositivo / Recently a fast development in organic and hybrid photovoltaic field has been observed. Such devices are fabricated by organic semiconductors within components of a heterojunction, in which bulk heterojunctions obtained via interpenetrating networks at the sub-20-nm length scale. It permits the effective collection of photogenerated charge carriers even with low exciton diffusion length and low charge carrier mobilities. Therefore, the study of material properties and the interface modification are essential to improve the power efficiency of such devices. The goal of this work is to investigate heterojunctions of titanium dioxide (TiO2) and poly(3-hexyl thiophene) (P3HT) as active layers in hybrid photovoltaic devices. Such heterojunctions are attractive since the metaloxide can be nanostructured previous the infiltration of the polymer within the nanocrystalline phase, leading on large interfacial area with the possibility to tune the interfacial properties keeping the acceptor/donor character of the two components. Titania films were obtained from colloidal dispersions of anatase nanoparticles, while P3HT from its solution in 1,2-dichlorobenzene. The electrodes were indium-tin oxide (ITO) and gold (Au). Electrical and spectroscopic characterization shows the photovoltaic parameters, as well as absorption and photoluminescence, depends on post-production treatments, evidencing that heating induces conformational changes in the polymeric phase, changing the oxide/polymer interface. The introduction of carboxyl groups at 3-hexyl ramifications in P3HT permits better contacts between oxide and polymer by chemisorption, being favored by thermal treatment. Furthermore, the infiltration of the polymer within the nanocrystalline TiO2 leads on enhanced stability of the devices, working even six months after their preparation. Finally, in this work is also proposed the utilization of a interface modifier based on zinc phtalocyanine complex, which has extended the device absorption window up to the red/ near infrared, increasing light harvesting, and a transport study related to photocarriers generation and recombination process was carried out by photoconductivity action spectra

Esta tese de doutorado é resultado do estudo da fotocondutividade em materiais poliméricos, com particular enfoque em diodos poliméricos com camada ativa de derivados do poli (p-fenileno vinileno) (PPV): OC10-PPV, SY e MEH-PPV, em estrutura tipo sanduíche (ITO/polimérico/Metal) de camada única, utilizando eletrodos metálicos com diferentes funções trabalho depositados sobre o mesmo filme. Para isso, foi necessária a realização de todas as etapas de fabricação de dispositivos orgânicos, como descritas neste trabalho, para obter resultados com o máximo de reprodutibilidade, bem como o domínio das técnicas de caracterização. As propriedades ópticas dos filmes poliméricos foram analisadas através dos espetros de absorção e de fluorescência estacionária na região do visível. O comportamento fotocondutivo dos dispositivos foi realizado através de medidas de corrente-tensão (I-V) e da espectroscopia de fotocorrente no estado estacionário em regime dc sob incidência de luz com diferentes comprimentos de onda, ora através do ITO, ora através dos eletrodos metálicos semitransparente, para o dispositivo sob diferentes valores de tensões aplicadas. A variação desses parâmetros permitiu verificar como estes influenciam na fotogeração e no transporte de portadores de cargas e assim adaptar e aplicar um modelo teórico que levasse em consideração o campo elétrico aplicado para ajustar a fotocorrente obtida experimentalmente, obtendo informações sobre as propriedades de fotocondutividade dos materiais estudos. / This thesis is a study about photoconductivity in polymeric materials, in particular diodes with single-layer sandwich structure derivates of poly(para-phenylene vinylene) (PPV): OC10-PPV, SY and MEH-PPV. Different metallic electrodes were deposited on the same polymeric layer. Therefore, it was necessary to realize the devices fabrication process step by step as well to dominate the characterization techniques. The optical properties of polymeric film were analyzed through the absorption and emission spectrum in the visible region. The photoconductivity behavior was studied by dc current-voltage (I-V) and photocurrent action spectra through the absorption and emission spectrum in the visible region. The photoconductivity behavior was studied by dc current-voltage (I-V) and photocurrent action spectra through the both side of device under applied voltages. The variation of these parameters allowed verifying how are influencing in the charge carrier photo-generation and the charge transport and then to adapt and apply a theoretical model wich considers the electric field applied to fit the photocurrent action spectra of devices. The values of the parameters allow to survey important about photoconductivity properties of the materials

In donor-acceptor systems, ultrafast interfacial charge transfer (CT), charge separation (CS) and charge recombination (CR), are among the key factors in determining the overall efficiency of the optoelectronic devices. In this regime, precise knowledge of the mechanisms of these processes on the femtosecond scale is urgently required. In this dissertation, using femtosecond transient absorption and mid-Infrared spectroscopies along with steady-state absorption and emission measurements, we are not only able to address the fundamental understanding of these ultrafast dynamical processes, but also control them at various inter- and intramolecular electron donor-electron acceptor systems. In the photoinduced intermolecular charge transfer systems, where donor and acceptor are separated from each other, three systems have been investigated; cationic poly[(9,9-di(3,3′-N,N′-trimethylammonium) propyl fluorenyl-2,7-diyl)-alt-co-(9,9-dioctyl-fluorenyl-2,7-diyl)] diiodide salt (PFN) conjugated polymer donor with 1,4-dicyanobenzene (DCB) acceptor, negatively charged porphyrin (POS) donor with positively charged (PFN) acceptor, and finally, positively charged (PFN) donor with negatively charged graphene carboxylate (GC) acceptor. Based on studying these three systems, we were able to explore some important factors and deriving forces including chemical structure, electrostatic interactions, energy band alignment, hydrogen bonding and solvents with different polarities and capabilities for hydrogen bonding that influence the rate and efficiency of the charge transfer at the interfaces of these donor-acceptor systems. For instance, unlike the conventional understanding of the key role of hydrogen bonding in promoting the charge-transfer process, our results reveal that the hydrogen-bonding increases the spacing between the donor and acceptor units which significantly hinders the charge-transfer process. On the other hand, in the photoinduced intramolecular charge transfer systems, where donor and acceptor are chemically attached to each other, we investigate the effects of conjugation length on photoinduced charge transfer in π-conjugated oligomers naphthalene diimide (NDI) end-capped oligo(phenylene ethynylene)s (PEn-NDI), and poly-(phenylene ethynylene) (PPE) donor backbone with (NDI) acceptor end-caps (PPE-NDI-n) systems. The results of femtosecond transient absorption and mid-IR spectroscopies show that the charge separation occurs on the 1-10 ps time scale with the rates decreasing as oligomer length increases in PEn-NDI system. In addition, in PPE-NDI-n system, the fluorescence quenching measurements indicate very efficient photoinduced electron transfer from the PPE backbone to the NDI end-groups, and the transfer efficiency increases with decreasing the number of units. Finally, the new physical insights reported in this thesis provide an understanding of several key variable components involved, thus paving the way toward the exploitation of efficient charge transfer at donor-acceptor interfaces, which is the key element and urgently required for optimal optoelectronic-device performance.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22661号 / 工博第4745号 / 新制||工||1741(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 山子 茂, 教授 田中 一生, 教授 村田 靖次郎 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22891号 / 工博第4788号 / 新制||工||1749(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 田中 一生, 教授 秋吉 一成, 教授 古賀 毅 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23223号 / 工博第4867号 / 新制||工||1760(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 大北 英生, 教授 辻井 敬亘, 教授 田中 一生 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(工学) / 甲第23227号 / 工博第4871号 / 新制||工||1760(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 田中 一生, 教授 秋吉 一成, 教授 古賀 毅 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM