Over the past decade, graphene/nanomaterial hybrids have gained a great interest in various applications due to their unique optical properties. This work explores lanthanide doped upconverting nanoparticles (UCNPs)/graphene hybrid nanomaterials. Here, core/shell structures comprising β-NaGdF4:Y b3+(20%),Er3+(2%)@NaGdF4 and α-NaGdF4:Y b3+(20%), Er3+(2%)@NaGdF4 with oleate as capping agent were synthesized and characterized. The choice of lanthanide ions (Yb3+ and Er3+) and their concentrations plays an important role to make these nanoparticles undergo two optical processes (upcoversion and downshifting) capable to convert near-infrared excitation to visible and near-infrared emission. In order to make hybrid systems, these nanoparticles were combined with graphene films. The morphology and the optical behavior of the hybrid samples were studied by microscope and hyperspectral imaging. The multi-energy sublevels from the 4f electronic configuration of lanthanides, their long excited state lifetime and the high carrier mobility of the graphene expected to open an exciting possibility of interaction, however, UCNPs/Graphene hybrid nanomaterial exhibits a minimal response when subjected to 980 nm laser illumination.

<p>The discovery, formulation, and characterization of novel compositions of matter for aid in the diagnosis and treatment of disease has ever been a compelling force behind nanomaterials development. In instances of disease originating from oncogenic mutation, proliferation, and metathesis; cancer has long been a most difficult dysfunction to diagnosis and treat in virtue of its innate alteration and disregulation of otherwise well-managed and healthful cellular processes. To date, cancer therapies have relied largely on highly toxic chemotherapy or radiation treatments, addressing the overarching problem of individual cellular mutations in a global sense, often deleterious to the overall health of the patient. Ever-progressing work on nanomaterial-based applications to either promote cancer diagnosis or implement novel therapeutic means of drug delivery, activation, or the precisely-targeted destruction of cancer cell lines has been afforded much attention in the integrated biological and materials science fields. Recent developments in nanosized laser materials incorporating lanthanide-doped sensitizer and activator pairs and the development of numerous crystallographic, co-dopant, morphological, and/or surface-appended optimizations to these materials have given rise to a novel class of nanomaterials, with unique photophysical properties that have direct import into light-based activation of chemical processes, triggered non-invasively through biological tissues, and merging intra-cellularly targetable nanocrystalline compositions and ex vivo light activation. Upconverting nanocrystals (UCNCs) are one such class of nanomaterial wherein near-infrared (NIR) light, at the nadir of tissue absorption, can serve to sequentially or cooperatively excite long-lived lanthanide (Ln3+) 4f excited states and, through various energy transfer processes coupled between both the UCNC material composition and its integral Ln3+ dopants, are capable of building an excited state population capable of emitting in higher frequencies than its incident NIR excitation.</p><p>In the study of these UCNCs, the prospect of activating intra-cellular photodynamic processes or drugs of low cellular toxicity, until light activated in a precisely localized regime (e.g. the nucleus of a cell), has motivated extensive research into the generation of novel UCNC materials, in multiple compositions and on multiple size scales to direct the mechanisms of upconversion (UC) to produce high fluence ultraviolet (UV) photons upon NIR (972 nm) excitation. Continuing optimizations have yielded a high ytterbium (Yb) sensitizer, cubic &#945;-NaYbF4 UCNC composition, codoped with a thulium activator, to generate excited state saturated UV transitions, 1I6 &#8594; 3F4 (349 nm) and 1D2 &#8594; 3H6 (362 nm), and their refinement to afford dominant UV emissive spectral signatures at low NIR laser excitation. Their photophysical dynamics are sparsely described in the literature, breaking from both fields of laser photonics and conventional inorganic nanoscience, and require renewed emphasis to be afforded in exacting crystallographic, photophysical, and size dependent effect characterization, heavily directing the structure-function relationships of luminescent Ln3+ dopants and their host crystal matrices. Requisite in this study is a call for the optimization of uniform, monodisperse, and reproducible preparations of unique UCNCs and precise characterization of the properties they display and the origins thereof.</p><p>Offered herein are the enveloping efforts to more fully understand the mechanistic processes of UC of both poorly characterized, literature standard materials, novel UCNCs tuned for enhancement of UC emission in the UV, and the adaptations to each that ultimately affect their photophysical dynamics. A tandem course of this research follows from inorganic shelling, passivation methodologies to ameliorate crystallographic surface defects and UC luminescence quenching sites to overall enhance the dominant UV emissivity of novel co-doped UCNC. These state-of-the-art UC materials are: 1) &#945;-NaYbF4: Tm3+, interlaced with gallium, chromium, yttrium, and other trivalent metal ions, serving to finely modulate UC mechanistic processes and enhance luminescent properties and 2) sodium co-doped LaF3 and BaLaF4 (0.5%Tm, 20%Yb), displaying 3 and 2 orders of magnitude enhancement of UV emissions due to controlled perturbation of the local crystal field environment. The Core @ Shell architectural derivatives of these materials exhibit an eminent departure from classical luminescent fluorophores, phosphors, or quantum confined luminescent nanomaterials, in both degree of luminescent flux generation and the complicated mechanistic processes they are derived from.</p><p>To a great extent, this work attempts to establish testable grounds for comparison of UCNCs; extending from interrogation of photophysical lifetime measurements, excitation versus emissive flux power dependence studies, high resolution X-ray photoelectron spectroscopy (HR-XPS) and power diffraction (HR-XRD) assessments of crystallographic defects and perturbations on the atomic scale, and the establishment of new metrics of radiant flux versus absolute quantum yield for use in comparison of UCNCs towards their applicability in areas of variable or limited excitation flux and the ultimate utility of discerning hit-to-lead UCNC materials for medical nanodevice compositions. A salient component affecting these metrics is the direct surface interactions with respect to solvents, coordinating ligands, and appended functional moieties for enhancement of UCNCs towards specific applications; largely directed towards cancer biology and medical study. In a confluence of inquisition of UCNCs and their high energy, UV luminescent properties, interfacing with the surface presenting effects of solublization and bio-targeting molecular functionalization; literature standard, &#946;-NaYF4 (2%Er, 20%Yb) UCNCs have been generated in highly uniform compositions to assess the size-dependent effects with respect to luminescent quenching surrounding a UCNC surface and functionalization methodologies have been offered as a proof of concept towards the construction of an optimized biomolecular targeting nanodevice, with known limits and predictable interactions, both to NIR excitation light and potential intra-cellular biological environments.</p><p>The ultimate goal of these explorations is the innovative fusion of the above concepts into a nanotherapeutic device involving: 1) the generation of a well-studied and predictable NIR-absorbing and dominant UV-emissive UCNC, with defined co-dopant optimizations and employing an optimal Core @ Shell architecture, 2) the requisite surface functionalization needed to afford aqueous solubility and a means of covalently conjugating targeting molecules of interest, and 3) the ultimate and equal assessment of such a composite system with respect to possible alternate materials in the literature and novel UCNCs currently under development. To date, no such convergent study has been conducted to any degree of reproducibility or certainty of desired and defined functionality. In this work is described in detail each optimized component for such a device or potentially one marked by differing, but assessable conditions for alternate applications. The optimization of a sub-10 nm, dominant UV-emissive UCNC, the crystallographic and photophysical origins of its UC mechanism under varied conditions, and the optimal means of their employment (both in terms of establishing equivalent metrics and utility in cancer nanotherapeutics), assessment, and readdressing of, as yet undiscovered limits to these materials are presented.</p> / Dissertation

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La haute sensibilité et l’analyse simultanée de plusieurs biomarqueurs (multiplexage) sont des enjeux essentiels pour permettre des avancées significatives pour le diagnostic médical. De telles avancées permettraient d’augmenter la précocité des diagnostics pour de nombreuses maladies comme le cancer ou des maladies cardiaques. Les immunodosages de FRET (transfer d’énergie par resonance de type Förster) sont basées sur la reconnaissance de biomarqueurs par des anticorps marqués avec des fluorophores et le FRET qui résulte du processus de reconnaissance immunologique. Aujourd’hui des telles immunodosages sont établis en utilisant des lanthanides comme donneurs de FRET et des fluorophores organiques comme accepteurs de FRET. Néanmoins, ils ne permettent pas de réaliser un multiplexage efficace car l’utilisation de plusieurs différents fluorophores organiques résulte dans un recouvrement spectral. Ce projet a pour but de mettre en application les propriétés optiques exceptionnelles des complexes de terbium (Tb) et des boîtes quantiques (QDs) pour parvenir à des analyses biologiques de FRET multiplexées et ultrasensibles. Nous avons également étudié les propriétés optiques et morphologiques de nouvelles nanoparticules à conversion ascendante de type coeur et coeur/coquille dopées à l'ytterbium (Yb) et des ions d'erbium (Er) comme donneurs de FRET. / Combining high sensitivity with simultaneous analysis of numerous biomarkers (multiplexing) is an essential requirement for significantly improving the field of biomedical diagnostics. Such progresses would allow earlier diagnosis, which is required for numerous diseases such as cancer or cardiac diseases. FRET-immunoassays are based on biomolecular recognition events that occur between biomarkers and two specific antibodies conjugated with different fluorophores. The spatial proximity of the two fluorophores can lead to Förster resonance energy transfer (FRET), which can be detected for biomarker quantification. To date, such assays are established using lanthanide complexes as FRET donors and fluorescence dyes as FRET acceptors. However, these assays do not provide sufficient multiplexing capability due to spectral overlap, when several acceptor dyes are used. This project aims at exploiting the exceptional photophysical properties of terbium complexes (Tb) and semiconductor quantum dots (QDs) to provide ultrasensitive multiplexed FRETimmunoassays. We also studied the optical and morphological properties of novel core and core/shell upconverting nanoparticles doped with ytterbium (Yb) and erbium (Er) ions as possible FRET-donors for biosensing.

Cette thèse décrit le développement de nouvelles méthodes pour obtenir des nanoparticules fonctionnelles polyvalentes qui peuvent potentiellement être utilisées pour des applications biomédicales telles que la vectorisation de médicaments, des essais biologiques et la bio-imagerie. Les nanomatériaux sont des outils polyvalents qui ont trouvé des applications comme vecteurs de médicaments, la bio-imagerie ou les biocapteurs. En particulier, les nanoparticules de type core-shell ont attiré beaucoup d'attention en raison de leur petite taille, une relation surface/volume élevée, et une biocompatibilité. Dans ce contexte, nous proposons dans la première partie de la thèse (Chapitre 2), une nouvelle méthode pour obtenir des nanoparticules core-shell via la polymérisation radicalaire en émulsion et vivante combinées. Des particules cœurs de polystyrène de 30 à 40 nm, avec une distribution de taille étroite et portant à la surface des groupements iniferter ont été utilisés pour amorcer la polymérisation supplémentaire d'une couche de polymère. Des nanoparticules core-shell ont été préparées de cette façon. Différents types d’enveloppes : anionique, zwitterioniques, à empreintes moléculaires, thermosensibles, ont ainsi été greffées. Notre méthode est une plate-forme polyvalente permettant d'ajouter des fonctionnalités multiples soit dans le noyau et/ou l'enveloppe pour les études d'interaction cellulaire et de toxicité, ainsi que des matériaux récepteurs pour l'imagerie cellulaire. Dans la deuxième partie de la thèse (Chapitre 3), nous décrivons un procédé nouveau et polyvalent pour la modification de surface des nanoparticules de conversion ascendante (UCP). Ce sont des nanocristaux fluorescents dopés de lanthanides qui ont récemment attiré beaucoup d'attention. Leur fluorescence est excitée dans le proche infrarouge, ce qui les rend idéales comme marqueurs dans des applications biomédicales telles que les tests biologiques et la bio-imagerie, l'auto-fluorescence étant réduite par rapport à des colorants organiques et les quantum dots. Cependant, les UCP sont hydrophobes et non-compatible avec les milieux aqueux, donc une modification de leur surface est essentielle. La stratégie que nous proposons utilise l'émission UV ou visible après excitation en proche infrarouge des UCP, comme source de lumière secondaire pour la photopolymérisation localisée de couches minces hydrophiles autour les UCP. Notre méthode offre de grands avantages comme la facilité d'application et la fonctionnalisation de surface rapide pour fixer divers ligands, et fournit une plateforme pour préparer des UCP encapsulée de polymères pour des différentes applications. Des hydrogels stimuli-sensibles sont des matériaux qui changent leurs propriétés physicochimiques en réponse à des stimuli externes tels que la température, le pH ou la lumière. Ces matériaux intelligents jouent un rôle critique dans des applications biomédicales telles que la vectorisation de médicaments ou l'ingénierie tissulaire. La troisième partie de cette thèse (Chapitre 4) propose un nouveau procédé de préparation d'hydrogels photo et pH sensible. Deux composantes, l'un photosensible à base dl'acide 4-[(4-méthacryloyloxy) phénylazo] benzoïque et l'autre cationic contenant des unités 2-(diéthylamino)éthyl méthacrylate, ont été synthétisés. Leur association donne des particules monodispersées de 100 nm photo et pH sensibles. Ces nanoparticules peuvent être potentiellement utilisées pour la vectorisation de médicaments, en particulier de biomolécules telles que protéines ou siARN. En conclusion, nous avons conçu plusieurs nouvelles méthodes efficaces, polyvalentes, génériques et facilement applicables pour obtenir des nanoparticules et nanocomposites de polymères fonctionnels qui peuvent être appliqués dans de différents domaines biomédicaux comme la vectorisation de médicaments, les biocapteurs, les tests biologiques et la bio-imagerie. / This thesis describes the development of novel methods to obtain versatile, functional nanoparticles that can potentially be used for biomedical applications such as drug delivery, bioassays and bioimaging. Nanomaterials are versatile tools that have found applications as drug carriers, bioimaging or biosensing. In particular, core-shell type nanoparticles have attracted much attention due to their small size, high surface to volume ratio and biocompatibility. In this regard, we propose in the first part of the thesis (Chapter 2), a novel method to obtain core-shell nanoparticles via combined radical emulsion and living polymerizations. Polystyrene core seeds of 30-40 nm, with a narrow size distribution and surface-bound iniferter moieties were used to further initiate polymerization of a polymer shell. Core-shell nanoparticles were prepared in this way. Different types of shells : anionic, zwitterionic, thermoresponsive or molecularly imprinted shells, were thus grafted. Our method is a versatile platform with the ability to add multi-functionalities in either the core for optical sensing or/and the shell for cell interaction and toxicity studies, as well as receptor materials for cell imaging. In the second part of the thesis (Chapter 3), we describe a novel and versatile method for surface modification of upconverting nanoparticles (UCPs). UCPs are lanthanide-doped fluorescent nanocrystals that have recently attracted much attention. Their fluorescence is excitated in the near infrared, which makes them ideal as labels in biomedical applications such as bioimaging and bioassays, since the autofluorescence background is minimized compared to organic dyes and quantum dots. However, UCPs are hydrophobic and non-compatible with aqueous media, therefore prior surface modification is essential. The strategy that we propose makes use oft he UV or Vis emission light of near-infrared photoexcited upconverting nanoparticles, as secondary light source for the localized photopolymerization of thin hydrophilic shells around the UCPs. Our method offers great advantages like ease of application and rapid surface functionalization for attaching various ligands and therefore can provide a platform to prepare polymeric-encapsulated UCPs for applications in bioassays, optical imaging and drug delivery. Stimuli responsive hydrogels are materials that can change their physico-chemical properties in response to external stimuli such as temperature, pH or light. These smart materials play critical roles in biomedical applications such as drug delivery or tissue engineering. The third part of the thesis (Chapter 4) proposes a novel method for obtaining photo and pH-responsive supramolecularly crosslinked hydrogels. Two building blocks, one containing photoresponsive 4-[(4-methacryloyloxy)phenylazo] benzoic acid and the other, consisting of cationic 2-(diethylamino)ethyl methacrylate units, were first synthesized. Combining the two building blocks yielded photo and pH responsive monodisperse 100-nm particles. These nanoparticles can be eventually utilized for drug delivery, especially delivery of biomolecules such as siRNAs or proteins. In conclusion, we have designed several new efficient, versatile, generic and easily applicable methods to obtain functionalized polymer nanoparticles and nanocomposites that can be applied in various biomedical domains like drug delivery, biosensing, bioassays and bioimaging.

Solar-driven photocatalysis is of great interest in terms of a sustainable use of energy and its application in wastewater treatment. The UV light-driven photogeneration of H2O2 by solar irradiation is an advanced strategy for the treatment of bacteria and recalcitrant pollutants in wastewater, but suffers from low efficiencies. In this work, a solar-driven multifunctional nanocomposite consisting of Tm3+ upconverting nanoparticles, poly(vinyl alcohol), poly(acrylic acid) and hydroxylated sulfonated poly(ether ether ketone) was prepared. The components were crosslinked via a heating treatment at 170 °C, resulting in a non-leaching porous material. This nanocomposite exhibited excellent adsorption ability (89 % in 150 min) toward a 100 mg/L ciprofloxacin aqueous solution and proved to photodegrade it (50 %) upon 4 h artificial solar irradiation, exploiting photon upconversion processes. Moreover, an 80 % bactericidal effect against E. coli was registered upon sunlight irradiation. Altogether, these results suggest the feasibility of a solar-driven wastewater treatment based on upconverting nanoparticles.