Proefschrift Rijksuniversiteit Groningen. / Met lit.opg. - Met samenvatting in het Nederlands.

La nanotechnologie est devenue un domaine clé de la technologie du XXIe siècle. L’important développement des approches pour la synthèse des nanoparticules (NPs) avec une composition, une taille et une forme désirées rend compte du potentiel de leur utilisation comme « blocs de construction » pour des structures de plus grande échelle. Cela permet d’envisager à la fois la fabrication de matériaux fonctionnels et de dispositifs directement à partir de colloïdes par approche ascendante et la conception de matériaux sur plusieurs échelles de grandeur. Le procédé utilise l'assemblage ou l'auto-assemblage de NPs et conduit à des matériaux avec des architectures différentes notamment 1D (bâtonnets), 2D (films) ou 3D (super-réseaux ou gels). Cependant, la plupart des assemblages 3D sont limités à l'échelle micrométrique et sont difficiles à contrôler. Pratiquement, la seule voie permettant la préparation de structures 3D macroscopiques à partir de NPs est la gélification et la préparation d'aérogels. Une voie alternative consiste à disperser les NPs dans une matrice, conduisant ainsi à un matériau composite massif, avec des NPs non agrégées distribuées de manière homogène.Le présent travail est consacré au développement de matériaux à partir de NPs d'oxydes métalliques (principalement Y3Al5O12: Ce et Li4Ti5O12) de différentes dimensions et pour diverses applications. La première partie de ce travail décrit la synthèse de NPs de YAG: Ce et de LTO par approche glycothermale. Dans le cas du YAG: Ce, les conditions de réaction ont été ajustées de façon appropriée pour obtenir des nanocristaux (NCs) non agrégés de quelques nanomètres. Des solutions colloïdales de différentes concentrations contenant de tels NCs ont été utilisées, pour la fabrication par la technique de « spin-coating », de films minces avec une épaisseur contrôlable. A l’inverse, la synthèse de LTO conduit à des NPs agrégées dans une structure hiérarchique très bénéfique pour les batteries au lithium. La grande surface spécifique et la porosité du matériau obtenu assurent en effet un échange efficace des ions lithium entre l'électrolyte et le matériau d'anode.Par ailleurs, les NCs de YAG: Ce ont été utilisés pour la préparation de matériaux monolithiques de grande taille avec une porosité et une transparence élevées. Pour cela, la solution colloïdale de NCs a été gélifiée par le changement brusque de la constante diélectrique du solvant de dispersion des NCs. Les gels ainsi obtenus ont été par la suite séchés de manière supercritique, donnant ainsi des aérogels à base de NPs de YAG:Ce, avec une porosité et une transparence élevées. La même approche s'est avérée appropriée pour d'autres systèmes à base de NPs de GdF3 ou de mélanges de NPS de YAG: Ce et de GdF3.Alternativement, les NPs de YAG: Ce ont été incorporées dans des aérogels de silice formant ainsi des aérogels macroscopiques robustes et hautement transparents présentant les propriétés des NPs incorporées. Ces aérogels composites ont été utilisés en tant que nouveaux types de capteurs pour les rayonnements ionisants de basse énergie dans les liquides ou les gaz. Leur porosité élevée permet un contact optimal entre l'émetteur radioactif et le scintillateur assurant ainsi une bonne récupération de l'énergie radioactive. / Nanotechnology has become a key domain of technology in XXI century. The great development of the synthetic approaches toward nanoparticles (NPs) with desired composition, size and shape expose the potential of their use as building blocks for larger scale structures. It allows fabrication of functional materials and devices directly from colloids by bottom-up approach, thus involving possibility of material design over several length scales. The process is referred to NPs assembly or self-assembly and leads to materials with varying architectures as for instance 1D (rods), 2D (films) or 3D (superlattices or gels). However most of 3D assemblies are limited to the micrometric scale and are difficult to control. Practically the only route allowing preparation of macroscopic 3D structures from NPs is their gelation and preparation of aerogels. As an alternative, NPs can be embedded in some matrix creating bulk composite material, with homogenously distributed non-aggregated NPs.Therefore, this work is devoted to development of materials with different dimensionalities for various applications from metal oxides NPs (mainly Y3Al5O12:Ce and Li4Ti5O12). The first part describes the syntheses of YAG:Ce and LTO NPs by glycothermal approach. In the case of YAG:Ce, the reactions conditions were appropriately adjusted in order to obtain non-aggregated nanocrystals (NCs) of few nanometers. The colloidal solution containing such NCs with different concentration was used for fabrication of thin films with controllable thickness by spin-coating method. Contrary, the synthesis of LTO led to aggregated NPs with hierarchical structuration which was highly beneficial for Li-ion batteries. The large surface area and porosity ensured efficient exchange of Li ions between electrolyte and anode material. Furthermore, the YAG:Ce NCs were used for preparation of macroscopic monoliths with high porosity and transparency. For that reason, colloidal solution of NCs was gelled by the abrupt change of solvent dielectric constant. The gels were further supercritically dried yielding YAG:Ce NPs-based aerogels with high porosity and transparency. The same approach turned o be appropriate for other systems like GdF3 or hybrid aerogels of YAG:Ce and GdF3.Alternatively, YAG:Ce NPs were incorporated into silica aerogels forming robust macroscopic and highly transparent aerogels exhibiting properties of incorporated NPs. They served for novel type of sensors for low-energy ionizing radiation in liquids and gases. Their high porosity assured well-developed contact between radioactive emitter and the scintillator ensuring good harvesting of radioactive energy.

La nanostructure et les propriétés électroniques de matériaux modèles pour le photovoltaïque organique, ont été étudiées en utilisant la Microscopie à Force Atomique en mode non contact sous ultra-vide (NC-AFM) et la Microscopie à sonde de Kelvin (KPFM). En utilisant le mode modulation d'amplitude (AM-KPFM), le potentiel de surface photo- généré dans des mélanges donneur-accepteur présentant une ségrégation de phase optimale a pu être visualisé à l'échelle du nanomètre. Afin de préciser la nature des forces mises en jeu dans le processus d'imagerie KPFM, des oligomères π-conjugués auto-assemblés ont ensuite été étudiés. Une transition entre régimes à longue et à courte portée a ainsi été mise en évidence en combinant l'imagerie en haute résolution aux mesures de spectroscopie en distance. Ces mesures ont également démontré que l'influence des forces électrostatiques à courte portée peut être minimisée en travaillant au seuil du contraste de dissipation. Enfin cette procédure a été utilisée, en combinaison avec les mesures de spectroscopie de photoélectrons UV, pour analyser la fonction de sortie locale d'électrodes transparentes à base de nanotubes de carbone fonctionnalisés. / In this thesis, noncontact atomic force microscopy (NC-AFM) and Kelvin probe force microscopy (KPFM) under ultrahigh vacuum have been applied to investigate the nanostructure and electronic surface properties of model materials for organic photovoltaics. First, it has been demonstrated that the surface photovoltage of nanoscale phase segregated donor-acceptor photovoltaic blends can be finely resolved at the nanometer scale by using amplitude modulation KPFM (AM-KPFM). Next, model self-assembled π-conjugated oligomers have been investigated, in order to obtain a deeper insight into the nature of the tip-surface forces involved in the KPFM imaging process. A crossover between long-range (LR) and short-range (SR) regimes has been evidenced by combining high resolution imaging with distance-spectroscopy measurements. It has also been shown that the influence of the SR electrostatic forces can be minimized by working at the onset of the damping contrast. Finally, using this procedure, the local work function of flexible transparent electrodes, comprised of functionalized carbon nanotubes by metallic nanoparticles, has been investigated, and compared to the averaged value deduced from ultraviolet photoelectron spectroscopy.

(FOR FIGURES REFER THE MAIN PDF FILE) Supramoleculr chemistry, aptly termed by Lehn as the study of molecular sociology, is the chemistry of the intermolecular bond, focusing on the structures and functions of “supermolecules” –chemical system formed by the association between two or more molecular components. While interrelated, this discipline forges beyond the domain of traditional molecular chemistry, which seeks to master the manipulation of the covalent bond between atoms and uncover the principle that governs the structures and properties of molecular species. Supramolecular chemistry assayas to blend the comprehensive resources of molecular chemistry with designed control of the intermolecular interactions to engineers supramolecular with features as well defined as those of the constituent molecular themselves. Not surprisingly, it has been stated that supramoleculars are to molecules and the intermolecular bond what molecules are to atoms and the covalent bond. In the realm of molecular crystals, the focus of supramolecular chemistry and indeed, the scope of the present thesis coverings with that of a rather recent, but rapidly emerging scientific discipline, namely crystal engineering. Coined nearly four decades ago in connection with photodimerization reaction in crystalline cinnamic acids, the term” crystal engineering” has since then broadened its expanse considerably and is, at present, most appropriately defined as“the understanding of intermolecular interactions in the context of crystal packing and the utilization of such understanding in the design of new solids with desired physical and chemical properties”. It would be befitting to remark that it is very pursuit (and more often than not, the elusive target) of being able to make functional solids by design that has allowed crystal engineering to evolve from an object of mere Scientific curiosity to a subject of tremendous utilization value. No proof for this assertion might be greater than that which lies in the fervent efforts put forth by pharmaceutical companies in understanding and controlling drug polymorphism, especially in the wake of the contemporary legal implications attendant with observing such a phenomenon. Polymorphism in molecular crystals results from the possibility of at least two different arrangements of the molecular of a given compound in the solid state and has therefore often been regarded as the” dark side” of crystal engineering. On one hand, polymorphism presents itself as an important probe in the study of structure-property relationship and allows elucidation of the varied macroscopic properties of the same molecule self-assembled in different crystalline environments. On the other hand, the phenomenon poses an implicit complication when predicating the product of a crystallization process forms the goal of a crystal engineering project. This is particularly true in case of crystal structure prediction (CSP) from the molecular structure of a given compound, where the experimentally obtained polymorphic modification may be a kinetic form and therefore, need not correspond to the one ranked lowest in energy from the computational studies. Indeed, this dichotomy between a thermodynamically and a kinetically controlled crystallization process reflects the underlying uncertainty associated with judging the outcome of a crystallization event. In this concept of a supramolecular synthon has been postulated to assimilate both thermodynamic and kinetic alternative, and therefore provide a working model for heuristic crystal design. By analogy with corey’s definition of a molecular synthon, a supramolecular synhon has been described” a structural unit within a supramolecule which can be formed and/or assembled by known or conceivable synthetic operations involving intermolecular interactions”. Being entirely probabilistic in nature, the robutness and thus, the transferability of a particular synthon to a designed crystal is assessed from a systermatic evolution of its recurrence in crystal structures of representative molecules. The Cambridge Structural Database (CSD), which announced the inclusion of the 500000th crystal structures in its archives last year, provides an invaluable cache of experimentally determined structures and the foundation for crystal design in this regard. The practically of the supramolecular synthon approach, now almost synthymous with crystal engineering, has been demonstrated not only in the successful design of a number of functional solids, but also in its possible application in CSP as a knowledge-based alternative. Irrespective of the approach, a basic paradigm can however be constructed from any crystal engineering strategy, viz. construct the molecular building blocks and assemble these, with a prior knowledge of the possible non-covalent interactions, in a manner that leads to the desired crystal structure. This premise will form the central theme of the present thesis, entitled “From molecular to supramolecular: Probing solid state self –assemblies of conformatonally locked polycyclitos and structural siblings”. The dissertation will deal with the nuances of the self-assemblies of four classes of structurally related crystalline polycyclie compounds, all fashioned from a prototypical rigid trans-decalin backbone derived from commonly available aromatic precursors like naphthalene and anthracene. The thesis will be presented in four chapters, each based on one of the four functional make-ups present in the molecular under study. • Chapter 1.Relating intramolecular O-H…Ohydrogen bondigs to conformational locking: Design and self-assemblies of crystalline polyclitols. • Chapter 2.Preferences of supramolecular assemblies towards competing inter- and intramolecular O-H…O hydrogen bonds: A case study in crystalline acyldervaeives of conformarionally locked polyclitols. •Chapter 3.Synthesis of novel polyhydroxylated flustrates: Probing fluorine interactions in a conformatonally constructed environment. • Chapter 4. Strength vs.accessiblity: Universe the patterns of self-recognition in designer conformationally locked aminoacohols. A brief overview of each chapter is presented below. The first chapter of the thesis investigates the supramolecular chemistry of an O-H…O Hydrogen Bond formed between hydroxyl groups that have been constrained to occupy spatiality invariant position in the crystal structure of a polycyclitol (a portmanteau word derived from polycyclic cyclitol). Having been constructed on a grid trans-decalin carbocyclic backbone, the polycyclitols under study 1-6 are conformatonally locked and destined to exhibit an axial rich disposition of the hydroxyl groups, so that the OH functionalities in 1,3-relationship are automatically brought into a favorable geometry for the formation of intramolecular O-H…O hydrogen bonds. Working within this paradigm, which was formulated both logically and on the basis of the observed H-bonding patterns in the crystal structures of several conformationally locked polyols, we were able to demonstrate that intramolecular H-bonding between 1,3-syndisxial OH groups can be used as a tool to preordain the position of the intermolecular O-H…O-bond donors and accepts in the specially crafted polycyclitols 1-3. this observation not only simplified a qualitative visualization of the various packing patterns in 1-3, but also allowed us to propose, based on previously reported CSD analysis, the packing motifs mostlikely to converge with the experimental results. Despite its qualitative nature, the O-H…O hydrogen bonding patters, proposed for 1-3 were found to conform well with those observed experimentally for the tetrols 1 and 3, and even for the two polymorphic modifications of the hexol 2[Figure 1] The determination role played by intramolecular O-H…O bonding in the supramolecular assembly of 2, a novel bicycle C2h symmetric hexol having an all axial disposition of the six hydroxyl functionalities, prompted us to study the crystal packing of the three diastereomeric perhydro-2,3,4q,6,6,8a-naphthalenehexols 4-6. the end-to-end co-operative intramolecular O-H…O-H hydrogen bonding chain on both faces of the molecule, as observed in case of 2, through an axial-equatorial. Figure 1. (left) one of the packing modes proposed for the hexol 2. Note that the H-bonding pattern involves all donor/acceptor oxygen and incorporates infinite chains of O-H…O bonds of O-H….O bonds; (right) Molecular packing observed experimentally in the polymorph of the hexol 2 Transposition of one or more of the peripheral yhdroyl groups. With increased freedom now allowed to the OH groups in the choice of their H-bonding partners, as a compared to 2 crystal packing in the polycyclitols 4-6 evolved from the simplistic model of hydrogen bonding proposed and observed for 2,to ivoke more complex patterns of self assembly mediated through O-H…O-bonds In the second chapter, the crystal structures of four conformationally locked esters, namely tetraaccetate 7/tetrabenzoate 8 of hexol 2 and the diacetate9/dibenzoate 10 of tetrol1,have been analyzed in order to examine the preference of their supramolecular assemblies towards competing inter and intramolecular O-H…O hydrogen bonds. To this end, all the four esters under study were specially crafted on a trans-decalin backbone with the objective of relegating the O-H…O H-bond donors( in form of the 30 OH groups) to the molecular interior and having the peripheral H-bond accepters (in form of the 20 acyl groups) in 1,3-syndiaxial relationship. It was anticipated that this common design element would allow the supramolecular assembly of the easters to evolve along two possible pathway, namely one which employs intermoleculars O-H…O H-bonds (pathway 1) and the other that sacrifises those for intramolecular O-H…O H-bonds and settles for a crystal packing dictated by weak intermolecular interactions alone (pathway 2) A pure sample of 7 crystallized along pathway 1 in two enantiotropic modifications, one obtained at room temperature (form) and the other at 20 C0 (form) [Figure 2]. Behaving much like a temperature guided molecular switch, the tetraacetate 7 could be shifted reversibly between the forms response to changes in the ambient temperature. Thus, the form converted at -4 OC to the denser form, which displayed an unusual kinetic stability till 67 OC and transformed back to the form beyond this temperature. Subsequently, the close similarity between the self-assemble of the two dimonrphs of 7 and the diastereomer 11 was exploited in order to stimulated 7 to fallow the pathway 2 through preferential inhibition of pathway 1[Figure 3]. Interstingly, the nucleation inhibition 11 was obtained serendipitously a route 7 via an apparent breakdownof furst-platter rule. Unlike the tetraceatate 7, crystal packing in the tetrabenzoate 8 preferred to fallow exclusively pathway 2. The individualistic nature of the self-assemblies of 7 and 8 found to be in contrast commonalities noted in the mode of molecular assembly in 9 and 10 both of which conformed to a combination of pathway 1 and 2. A rationale for the preferred crystallization pathway of the four estes 7-10 as well as probable mechanism for the observed reversible transformation between the forms the tetracetate 7 will be put forth in this chapter. Figure 2. (Model for pathway 1) Molecular packing in the forms of the tetraacetate 7. The non-interacting hydrogen atoms have been omitted for clarity. Figure 3. (Model for pathway 2) The nucleation inhibitor 11 and form of the tetraacetate 7. The non-interacting hydrogen atoms have been omitted in the molecular packing diagram for clarity. In light of the wide ranging application of organofluorine compounds and the ambiguity that resides over the disposition of fluorine as a H-bond accepter, the third chapter utilizes three specially designed fluorinated polycyclitols 12-14 investigate the role of covalently bonded flurine in crystal structures of lesser studied aliphatic fluorous substracts and probe its capacity to engage itself in C(sp3)-F…H-X(sp3)(X=O and/or C) H-bounding, in presence of its isostere, the hydrozyl group. Conformatonality locked with well defined spatial disposition of functional groups, all the fluorinated polycyclitols 12-14 bear a fluorohydrin moiety, embedded in a rigid trans-decalin framework. In 12 and 14, it was conceived that the presence of a hydroxyl donor in a favorable 1, 3-syndiaxial relationship to a fluoro group on one side and a hydroxyl group on the other would allow an unambiguous comparison between the two isoteric functionalities (C-OH and C-F) to serve as acceptors for intramolecular hydrogen bonds (O-H…O and purported O-H…F respectively) The difluorodiol 13 was sought to serve as a control to assess the change in the C-F…H-X interactions (if any) which might be observed upon incorporating the peripheral secondary hydroxyl groups in 14. The result presented in this chapter will revel, in particular, that C(sp3) –F…H-C(sp3) hydrogen bonds, though weak and lesser investigated, can indeed be observed and supramolecular recognition motifs, involving such interactions, can be conserved even in crystal structures laden with stronger O-H…O hydrogen bonds [Figure 4}. Figure 4. (Left) Molecular packing in the difluorodiol 13, showing how four intermolecular C-H…F hydrogen bonds forms a part of a R22 H-bonding motif (encircled). This centrosymmentic supramolecular recognition unit is observed even in the molecular packing in the difluorohexol 14 (right). Non-interacting H atoms have been omitted in both diagrams for the sake of clarity. The forth chapter details an in-depth study carried out on the self-assembly of a conformationally locked aminoalchohol 15, in which the amino protons serve as mere spectators, the molecular packing in the crystal being realized through the co-operativity between O-H…N H-bonds and weak π-π stacking interaction (Figure 5b). The crystal structure of 15 was quite intriguing on three sailent grounds (a) previous studies on the supramolecular assemblies in the aminols have shown that both amino and hydroxyl protons participate in H-bonding in the crystal structures of such compounds; (b) the fact that the hydrogen atoms of the NH2 group Figure 5. (Left) Laplacian distribution map in the planes defined by (a) the double bonds, (c) O-H…N-H-bond, and (d) π-π stacking interactions in the aminoalclhol 15. Contours havse been drawn at logarithmic intervals in ▼2 ρb, eÅ-5. Solid lines indicate positive contours and dotted lines negative contours. (b) Molecular packing in 15. Non-interacting H atoms have been omitted for the sake of clarity.remain as mere bystanders in anomalous if one were to abide by the Etter’s rule; (c) the rather well-difined π-π stacking interactions in crystal structure of the aminoalcohol occurs between isolated olefinic bonds-a rarely encountered form of non-covalent interaction. Charge destiny analysis was carried out on the aminoalcoholf 15 not only to catheterize the non-covalent interactions existing in the supramolecular assembly in terms of topological features of electrol destiny at their bond critical points, but also to confirm the non-involvement of the amino H-atoms in any form of either intra- or intermoalecular hydrogen bonds beyond the criteria of mere geometry (Figure a,c,d). The maverick nature of the self-assembly of 15 was elucidated as resulting from the preference of the molecules to assemble with O-H…N H-bonds. This automatically relegated the hydrogen atoms of the tertiary amine to the interior of the conformationally locked cabocycclic scaffold, thereby making them far less accessible than the peripheral C=C bonds.

Les copolymères à blocs amphiphiles s’auto-assemblent en solution aqueuse grâce à l’association de leurs segments hydrophobes. Les nanoparticules formées à partir de copolymères biocompatibles et biodégradables tels que les poly(hydroxyalkanoates) (PHAs) sont particulièrement attractives pour la conception de systèmes à libération prolongée de principes actifs. La relation entre la composition/structure chimique du copolymère, ses propriétés d’auto-assemblage et ses effets sur les cellules in-vitro doit être étudiée. Des copolymères à blocs poly(acide malique)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB), PMLA-b-PHB-b-PMLA et poly(triméthylène carbonate)-b-poly(acide-malique) (PTMC-b-PMLA) ont été synthétisés par polymérisation par ouverture cycle (ROP) des monomères correspondants, suivie d’une hydrogénolyse. Une gamme de copolymères bien définis, caractérisés par spectroscopie RMN 1H, 13C{1H}, HSQC, HMBC, et DOSY, par analyses SEC, DSC, TGA, et mesure des angles de contact, présentant des balances hydrophile/hydrophobe modulables, a été obtenue grâce au control précis de la fraction hydrophile f (11-82%). Des auto-assemblages modulables ont été formés par nanoprécipitation des copolymères en l’absence d’agent tensio-actif. De larges agrégats ainsi que des micelles cœur-couronne (Rh = 16-335 nm) ont été obtenus en fonction du copolymère utilisé (dibloc vs. tribloc). Des micelles stables pendant 10 jours à 37 °C en solution aqueuse ont été obtenues pour les copolymères avec f allant jusqu’à 50%. Les copolymères PMLA-b-PHB et PTMC-b-PMLA n’ont pas révélé de toxicité aigüe in-vitro. De plus, l’utilisation du PHB a avantageusement permis de diminuer la captation des nano-objets par les macrophages et d’augmenter la captation par les cellules hépatiques. / Amphiphilic block copolymers are able to form self-assembled systems in aqueous solution by association of their hydrophobic segments. Nanoparticles formed from biodegradable and biocompatible polymers such as poly(hydroxyalkanoate) copolymers are particularly attractive for drug delivery applications. The relationship between the chemical structure/composition of the macromolecule, its self-assembly properties and its effect on cells in-vitro has to be studied.The synthesis of poly(-malic acid)-b-poly(3-hydroxybutyrate) (PMLA-b-PHB), PMLA-b-PHB-b-PMLA, and poly(trimethylene carbonate)-b-poly(-malic acid) (PTMC-b-PMLA) was established through the ring-opening polymerization (ROP) of the corresponding monomers followed by hydrogenolysis. A range of well-defined copolymers characterized by 1H, 13C{1H}, HSQC, HMBC, DOSY NMR spectroscopy, SEC, DSC, TGA, contact angle analyses, with tunable hydrophilic/hydrophobic balance were thus obtained through the precise control of the hydrophilic weight fraction f (11-82%). Tunable self-assembled systems were obtained by nanoprecipitation of the amphiphilic PHA-based copolymers without the use of a surfactant. Large aggregates and core-shell micelles (Rh = 16-335nm) were obtained depending on the polymer topology. PHB-based copolymers with f up to 50% formed highly stable micelles at 37 °C over a period of 10 days in aqueous solution. PMLA-b-PHB as well as PTMC-b-PMLA copolymers revealed no acute in-vitro cytotoxicity. The use of PHB as hydrophobic segment enabled to minimize the non-specific scavenging by macrophages cells while the cellular uptake by hepatocytes was favored.

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L’objectif de cette thèse était de mettre au point une analyse critique de vecteurs polymères utilisés pour la thérapie photodynamique (PDT) et de faire le lien avec l’efficacité thérapeutique observée. Pour cela, une analyse complète des vecteurs a été réalisée par des techniques classiques comme la diffusion dynamique de la lumière ou la microscopie électronique, mais aussi grâce au fractionnement flux-force, technique peu utilisée jusqu’à présent dans le domaine des auto-assemblages polymères. Dans un deuxième temps, les auto-assemblages ont été utilisés comme vecteurs d’un photosensibilisateur, le Phéophorbide a, et l’efficacité thérapeutique évaluée en travaillant sur culture cellulaire 2D et 3D de lignées HCT116 (cancer du colon) ou FaDu (cancer tête et cou). Différents vecteurs polymères simples ont tout d’abord été examinés, à savoir des micelles ou des polymersomes à base de copolymères diblocs amphiphiles comme le poly(oxyde d’éthylène-b--caprolactone), le poly(oxyde d’éthylène-b-lactide) ou le poly(oxyde d’éthylène-b-styrène). Ceci a permis d’obtenir des vecteurs présentant des tailles et des morphologies variables. Les résultats en PDT ont montré des comportements différents et une meilleure efficacité en 3D pour les systèmes à base de PEO-PDLLA. La technique de fractionnement flux-force asymétrique (AsFlFFF) a particulièrement été utilisée pour ces vecteurs afin de démontrer la pureté des auto-assemblages. Les connaissances acquises dans cette première partie ont permis de caractériser des vecteurs faits à base de mélanges d’auto-assemblages micelles/vésicules. Ceux-ci ont révélé des phénomènes d’antagonisme ou de synergie dans l’efficacité en PDT, démontrant l’existence de processus complexes au niveau de la réponse cellulaire.Des auto-assemblages figés par réticulation ont aussi été développés, caractérisés et examinés en PDT. Ils se sont avérés extrêmement intéressants pour la PDT sur les cultures cellulaires en 3D, démontrant une efficacité accrue comparée aux systèmes simples. La comparaison de ces résultats avec ceux obtenus en culture 2D pour les mêmes objets a de plus permis de mettre en évidence la différence entre ces deux modèles biologiques. Enfin, des auto-assemblages à base de complexes poly-ioniques ont aussi été formés et caractérisés. Le fractionnement flux-force s’est là encore avéré efficace, mais a nécessité l’utilisation d’une injection spéciale par Frit-inlet. Leur efficacité en PDT s’est avérée faible. / The objective of this study was to critically analyze different polymer self-assemblies used for photodynamic therapy (PDT) and to link this analysis to their therapeutic efficiency. To do that, a thorough characterization of the vectors has been performed by classical techniques such as Dynamic Light Scattering or electron Microscopy, but also using flow fractionation, which has been seldomly used so far for polymeric self-assemblies. In a second step, these have been used as vectors of a photosensitizer, namely Phéophorbide a, and the therapeutic efficiency assessed on both 2D and 3D cell cultures of HCT 116 (colon cancer) and FaDu (head and neck cancer) cells. Different simple polymer vectors have first been evaluated, namely micelles and polymersomes based on diblock amphiphilic copolymers such as poly(ethylene-oxide-b--caprolactone), poly(ethylene-oxide-b-lactide) or poly(ethylene-oxide-b-styrene). This enabled obtaining vectors exhibiting various sizes and morphologies. Results in PDT showed different behaviours and a better efficiency in 3D for PEO-PDLLA. The Asymmetric Flow Field Flow Fractionation was particularly used for these systems to demonstrate their purity. The acquired expertise on this part enabled us to also characterize vectors made of known mixtures of micelles and polymersomes. These revealed antagonism and synergy effects in PDT, demonstrating the presence of complex processes for the cell response. Other self-assemblies consisting of crosslinked systems have also been developed and characterized. These were observed to be particularly efficient for PDT on 3D cell cultures. The comparison of these results with those for the 2D cell culture enabled to highlight the difference between those two biological systems. Finally, self-assemblies based on Polyion Complexes were also formed and characterized. Field Flow Fractionation was once again used as a powerful technique for this, although this implied the use of a special injection device called Frit Inlet. Their PDT efficiency however proved to be low.