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Les nanoparticules seront sans doute les outils diagnostiques et thérapeutiques de demain. Si ellessont magnétiques, elles sont promises à des applications telles que le renforcement du contraste enIRM, la thermothérapie et la libération contrôlée de médicaments. Les nanomatériaux La1-xSrxMnO3ont été sélectionnés car leur température de Curie (TC) peut être ajustée dans la gamme detempérature thérapeutique. Des particules calibrées en taille et désagrégées ont été élaborées par leprocédé glycine-nitrate (GNP). Les caractérisations chimiques et structurales ont permis de mieuxcomprendre les résultats contradictoires de la littérature concernant la soi-disant dépendance de TCavec la taille des nanoparticules. L’adaptabilité de ces nanoparticules pour des applications enhyperthermie ou en IRM a été confirmée. Enfin, la capacité des nanoparticules à s’échauffer a étéutilisée pour réticuler autour d’elles une couronne de macromolécules thermosensibles selon leconcept nouveau de chimie localement stimulée. / Nanoparticles may be the next generation of diagnostic and therapeutic tools. If they are magnetic,they are dedicated to applications such as MRI contrast agent, thermotherapy and controlled drugrelease. La1-xSrxMnO3 nanoparticles were selected because their Curie temperature (TC) may be tunedwithin the range of therapeutic temperature. Size sorted and disaggregated particles weresynthesized by the Glycine-Nitrate Process. Chemical and structural characterizations allowed abetter understanding of conflicting results found in the literature about the particle size-dependenceof TC. The possibility to use these nanoparticles for hyperthermia and MRI applications has beenconfirmed. Finally, their ability to heat has been used to crosslink thermosensitive macromoleculesall around them according to the new concept of locally stimulated chemistry.

Nous avons synthétisé différentes dyades donneurs-accepteurs (D-A) π-conjuguées à base de fullerène pour des applications photovoltaïques dans lesquelles les unités D étaient soit des oligophenylenevinylenes (OPV) soit des oligophenyleneethynylene (OPE) et les unités A étaient le C60 ou un endofullerène du type Y3N@C80. Il y avait une exigence supplémentaire pour nos matériaux, à savoir qu’ils devaient s’auto-organiser en phases liquides-cristallines. Pour ce faire, toutes les unités D contenaient un promoteur mésogène afin d'induire le mésomorphisme de la dyade D- et donc de contrôler la morphologie des couches minces nécessaires à l’élaboraiton des cellules photovoltaïques grâce à une organisation supramoléculaire. En dehors de cela, nous avons étudié l’influence de la nature chimique du donneur (par exemple lyophile ou amphiphile), de la longueur des oligomères et de la multiaddition sur les propriétés photophysiques et sur l'auto-assemblage. Nous avons synthétisé une dyade OPE-Y3N@C80 qui est le premier dérive mésomorphe et photosensible de ce type de métallofullerène endohédral. / We have synthesized different π-conjugated system-fullerene dyads for photovoltaic applications, where the donor units were either oligophenylenevinylene (OPV) or oligophenyleneethynylene (OPE) derivatives and for the acceptor, C60 or Y3N@C80 was used. There was an additional requirement for our materials: liquid crystallinity. All the donor units contained a mesogenic promoter in order to induce mesomorphism in the D-A dyad and to control the morphology of the prepared film through supramolecular organization. Apart from that, we investigated the effect of the chemical nature of the donor moiety (ie. lyophilic or amphiphilic), the oligomeric length and multiaddition on the photophysical properties and on the self-assembly. We have synthesized an OPE-Y3N@C80 dyad which is the first trimetallic nitride template endohedral metallofullerene derivative with mesomorphic and photoactive properties.

A teragnóstica de doenças tem sido extremamente marcada nos últimos anos por nanomateriais formados pela conjugação de nanopartículas a biomoléculas, pois a aplicação de tecnologias baseadas em materiais na dimensão nanométrica é capaz de aumentar a seletividade, sensibilidade e praticidade dos métodos atualmente empregados, ou mesmo criar novos métodos de diagnóstico e tratamento de doenças. Dentre os vários tipos de nanomateriais desenvolvidos, aqueles baseados em nanopartículas de ouro ou nanopartículas magnéticas apresentam propriedades químicas e físicas diferenciadas que propiciam novas possibilidades. Por exemplo, a presente tese demonstrou que nanopartículas superparamagnéticas são excelentes agentes de contraste em exames de imagem por ressonância magnética (IRM) por serem mais seguros, apresentarem melhor contraste nas imagens e possibilitarem direcionar/concentrar o material em tecidos ou tumores através de um gradiente de campo magnético aplicado. Foram feitos numerosos ensaios de toxicidade tanto in vitro quanto in vivo para assegurar a segurança da aplicação de nanopartículas no organismo, cujo potencial de uso somente se tornará uma realidade caso os nanomateriais se mostrem não tóxicos e biocompatíveis. Apesar dos significativos avanços na área da aplicação desses nanomateriais, não foram encontrados na literatura modelos capazes de explicar ou prever por quais sítios de ligação devem ocorrer as interações proteína-nanopartícula, como também não foram encontrados estudos sistemáticos acerca dos fatores que determinam a estabilidade e a funcionalidade dos nanobioconjugados (NBCs). Assim, nesta tese buscamos compreender os fatores responsáveis pela ligação/adsorção das proteínas nas nanopartículas de ouro e sua influência sobre a estabilidade das suspensões e a funcionalidade das proteínas. Desta forma, foram obtidos NBCs com propriedades adequadas para o desenvolvimento ou aprimoramento de ensaios de diagnóstico e até para o tratamento de doenças. Foi demonstrado o potencial das nanopartículas de ouro para melhorar a performance de imunoensaios do tipo ELISA, mas também podem ser utilizadas para o desenvolvimento de métodos de diagnóstico, explorando as propriedades plasmônicas das nanopartículas de ouro acopladas a técnicas como SERS, SPR e microscopia Raman confocal. / Theranostics has been intensively pursued in recent years using hybrid materials based on nanoparticles conjugated with biomolecules. This is an interesting strategy to increase the selectivity and sensitivity, as well as to improve the currently used methods facilitating their use or creating new ones. Among the various types of nanomaterials, those based on gold and magnetic nanoparticles exhibit interesting chemical and physical properties in the biological environment, differing from that of free drugs or current explored in assay methods. For example, superparamagnetic nanoparticles are excellent contrast agents for magnetic resonance image (MRI) diagnostics because they are safer, present a better contrast efficiency for imaging and can be magnetically accumulated in tissues or tumors using a magnetic field. Numerous in vitro and in vivo toxicity assays were performed to ensure the safety for medical applications. Clearly, these type of applications only will be realized if nanomaterials prove to be nontoxic and biocompatible. This imply an strict control on their structure and composition. However, despite the significant advances in the development of such nanomaterials, there were not found in the literature model systems explaining or that can be used to predict by which sites the protein-nanoparticle binding should take place. In addition, no systematic studies on the factors determining the stability and the functionality of nanobioconjugates (NBC) were found. Thus, this thesis is focused in unveiling the factors responsible for binding/adsorption of proteins on gold nanoparticles and their influence on the colloidal stability of hybrid nanoparticles suspensions while keeping the functionality of biomolecules. In fact, NBC with enhanced properties suitable for the development of diagnostic methods and even for treatment of diseases were obtained. These nanomaterials can improve the ELISA immunoassay, or other diagnosis methods can be developed by using the gold nanoparticles plasmonic properties in association with SERS, SPR and confocal Raman microscopy techniques.

A teragnóstica de doenças tem sido extremamente marcada nos últimos anos por nanomateriais formados pela conjugação de nanopartículas a biomoléculas, pois a aplicação de tecnologias baseadas em materiais na dimensão nanométrica é capaz de aumentar a seletividade, sensibilidade e praticidade dos métodos atualmente empregados, ou mesmo criar novos métodos de diagnóstico e tratamento de doenças. Dentre os vários tipos de nanomateriais desenvolvidos, aqueles baseados em nanopartículas de ouro ou nanopartículas magnéticas apresentam propriedades químicas e físicas diferenciadas que propiciam novas possibilidades. Por exemplo, a presente tese demonstrou que nanopartículas superparamagnéticas são excelentes agentes de contraste em exames de imagem por ressonância magnética (IRM) por serem mais seguros, apresentarem melhor contraste nas imagens e possibilitarem direcionar/concentrar o material em tecidos ou tumores através de um gradiente de campo magnético aplicado. Foram feitos numerosos ensaios de toxicidade tanto in vitro quanto in vivo para assegurar a segurança da aplicação de nanopartículas no organismo, cujo potencial de uso somente se tornará uma realidade caso os nanomateriais se mostrem não tóxicos e biocompatíveis. Apesar dos significativos avanços na área da aplicação desses nanomateriais, não foram encontrados na literatura modelos capazes de explicar ou prever por quais sítios de ligação devem ocorrer as interações proteína-nanopartícula, como também não foram encontrados estudos sistemáticos acerca dos fatores que determinam a estabilidade e a funcionalidade dos nanobioconjugados (NBCs). Assim, nesta tese buscamos compreender os fatores responsáveis pela ligação/adsorção das proteínas nas nanopartículas de ouro e sua influência sobre a estabilidade das suspensões e a funcionalidade das proteínas. Desta forma, foram obtidos NBCs com propriedades adequadas para o desenvolvimento ou aprimoramento de ensaios de diagnóstico e até para o tratamento de doenças. Foi demonstrado o potencial das nanopartículas de ouro para melhorar a performance de imunoensaios do tipo ELISA, mas também podem ser utilizadas para o desenvolvimento de métodos de diagnóstico, explorando as propriedades plasmônicas das nanopartículas de ouro acopladas a técnicas como SERS, SPR e microscopia Raman confocal. / Theranostics has been intensively pursued in recent years using hybrid materials based on nanoparticles conjugated with biomolecules. This is an interesting strategy to increase the selectivity and sensitivity, as well as to improve the currently used methods facilitating their use or creating new ones. Among the various types of nanomaterials, those based on gold and magnetic nanoparticles exhibit interesting chemical and physical properties in the biological environment, differing from that of free drugs or current explored in assay methods. For example, superparamagnetic nanoparticles are excellent contrast agents for magnetic resonance image (MRI) diagnostics because they are safer, present a better contrast efficiency for imaging and can be magnetically accumulated in tissues or tumors using a magnetic field. Numerous in vitro and in vivo toxicity assays were performed to ensure the safety for medical applications. Clearly, these type of applications only will be realized if nanomaterials prove to be nontoxic and biocompatible. This imply an strict control on their structure and composition. However, despite the significant advances in the development of such nanomaterials, there were not found in the literature model systems explaining or that can be used to predict by which sites the protein-nanoparticle binding should take place. In addition, no systematic studies on the factors determining the stability and the functionality of nanobioconjugates (NBC) were found. Thus, this thesis is focused in unveiling the factors responsible for binding/adsorption of proteins on gold nanoparticles and their influence on the colloidal stability of hybrid nanoparticles suspensions while keeping the functionality of biomolecules. In fact, NBC with enhanced properties suitable for the development of diagnostic methods and even for treatment of diseases were obtained. These nanomaterials can improve the ELISA immunoassay, or other diagnosis methods can be developed by using the gold nanoparticles plasmonic properties in association with SERS, SPR and confocal Raman microscopy techniques.

Lanthanide elements display many remarkable and exciting properties which explain their widespread use in a number of very important biomedical tools like efficient MRI contrast agents or luminescent probes for highly sensitive assays of bioanalytes amongst other fields of application. In this context, the aim of the present work was to prepare and characterize lanthanide complexes of two ligands that feature a linear or a macrocyclic chelating unit compactly grafted onto a 1,10-phenanthroline derived moiety (phenDTPA and PhenHDO3A). The ditopic nature of the ligands allows the selective incorporation of a d6 metal ion and a lanthanide one in close proximity. The resulting rigid heterobimetallic supramolecular species show useful properties and constitute potential MRI contrast agents or new luminescent compounds depending on the type of the lanthanide and transition metal ions employed: for example, the selfassembly process of gadolinium(III) chelates around an iron(II) ion brings a remarkable increase of their relaxivity, a key parameter for use in MRI. On the other hand, association of a ruthenium and and a near infrared emitting 4f ion like ytterbium(III) gives mixed d-f structures able to harvest visible light and convert it into near infra-red signal. Visible light luminescent pH probes were also obtained with Eu3+ or Tb3+ phenHDO3A complexes.