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A major drawback of chemotherapy is the lack of selectively leading to damage in healthy tissue, which results in severe acute side effects to cancer patients. The use of nanoparticles as a drug delivery system has emerged as novel strategy to overcome the barriers of immunogenic response, controlled release of therapeutic, and targeting the toxicity only to cancerous cells. In this study, polymeric nanoparticles composed of transition metals and particles derived from natural biopolymers have been generated via self-assembly. For example, nanoparticles composed of cobalt crosslinked with albumin (Co-alb NPs) via Co-amine coordination chemistry of lysine residue were syntheisized in various sizes. The method to generate Co-alb NPs involves no thermal heat, organic solvent or any surfactants, which is ideal for the production of large amounts in a timely manner. The Co-alb NPs displayed exceptional stability under physiological conditions (pH 7.4) for several days with minor changes in size; however degradation could be triggered by reductant (reduced glutathione (GSH), 10 mM) with complete disappearance of particles in less than 2 hour. Numerous therapeutics that are highly effective toward cancer cells have been developed; however, many cannot be administered to patients due to poor solubility in water and pH dependent properties. We have successfully encapsulated 7-ethyl-10-hydroxycampothecin (SN-38) into Co-alb NPs with encapsulation efficiency as high as 94% and loading capacities greater than 30%. We employed an emulsion-solvent evaporation method to incorporate SN-38 into Co-alb (SN38 Co-Alb NPs). Release of the drug from SN38 Co-Alb NPs was determined for particles incubated in PBS or PBS-GSH. SN38 Co-Alb NPs were exceptionally stable under physiological condition (PBS pH 7.4), but exhibited sustained release of SN-38 over time in the presence of GSH. Uptake and toxicity of the particles were also investigated in a gastric carcinoma cell line (SNU-5) where high degrees of macropinocytic uptake were observed. The particles displayed significant toxicity making them a prime candidate for further testing in animal models.

Developing a sensitive and effective in vitro bioassay to detect endocrine disrupting chemicals (EDCs) would reduce the cost, eliminate the possibility of low dose effects, detect the non-monotonic dose responses, and identify mechanisms of actions. The “chemical nose” sensing method using supramolecular complexes composed of cationic monolayer functionalized gold nanoparticles (AuNPs) and fluorescent proteins (FPs) can successfully distinguish serum proteins, mammalian cells, tissue lysates, and chemotherapeutic drug mechanisms. EDCs regulate target cells via genomic or non-genomic pathways in terms of proliferative effect and response time. In this thesis, green fluorescent protein-gold nanoparticle (GFP-AuNP) sensors were used to detect the proliferative effect of 17b-estradiol (E2) and bisphenol A (BPA) on MCF7 and T47D cell lines at fM or pM dose range. Non-monotonic dose responses were also observed at different exposure times. The dose-response relationships using GFP-AuNP sensors could be correlated to the cell cycle analysis. Interestingly, tamoxifen, an estrogen antagonist, showed distinct patterns at low doses on HepG2 cells using triple channel FP-AuNP sensors, which might indicate different mechanisms of actions in this dose range.

Nanoparticles (NPs) have been used widely in various fields ranging from biomedical applications to life science due to their highly tunable properties. It is essential to understanding how NPs interact with biological systems of interest, therefore, analytical platforms to efficiently track NPs from cell to animal level are essential. In this thesis, laser desorption ionization mass spectrometry (LDI-MS) and inductively-coupled plasma mass spectrometry (ICP-MS) has been developed and applied to quantify NP/cell and NP/biological surface interactions. These two methods provide fast, label-free and quantitative analysis. New capability of LDI-MS to differentiate cell surface-bound and internalized NPs were established and ICP-MS coupled with a library of surface- functionalized AuNPs were used to probe the affinity between NPs and human hair surface. NPs interacting with biological surfaces and plasma membrane were quantified and the interactions were controlled by the chemical properties of the interface between NP and biological systems.

This thesis represents a major contribution to wideband and high gain inkjet-printed antennas on paper. This work includes the complete characterization of the inkjet printing process for passive microwave devices on paper substrate as well as several ultra-wideband and high gain antenna designs. The characterization work includes the electrical characterization of the permittivity and loss tangent for paper substrate through 10 GHz, ink conductivity data for variable sintering conditions, and minimum feature sizes obtainable by today’s current inkjet processes for metallic nanoparticles. For the first time ever, inkjet-printed antennas are demonstrated that operate over the entire UWB band and demonstrate gains up to 8dB. This work also presents the first fractal-based inkjet-printed antennas with enhanced bandwidth and reduced production costs, and a novel slow wave log periodic dipole array which shows minimizations of 20% in width over conventional log periodic antennas.

Understanding the dynamics of micro- and nanometer-sized objects like molecules, particles, and living cells in biological systems and biomaterials has become a key component in biomedical research. Consequently, significant progress has been made for the development of imaging platforms, fluorescent probes, and computational tools to visualize and quantify biological processes at different length and time scales. However, despite such advances, achieving a reliable measurement accuracy on the dynamic behavior of these microscopic vehicles in diverse biological contexts is challenging. Subsequently, the motivation behind this dissertation is to develop new robust microfluidic velocimetry techniques to investigate molecular transport and cell migration within an in-vitro microfluidic platform.

Current methods for preparing graphene quantum dots (GQDs) rely on oxidation and reducing agents or require energy-intensive and technologically demanding preconditions. Applying microwave expansion and liquid phase exfoliation (LPE) in a sample of graphite powder enabled us to prepare GQDs that exhibit strong luminescence in the blue region of the visible spectrum. The proposed technique for synthesizing GQDs is energetically undemanding and does not necessitate additional chemical components.

L’arrivée des nanobiotechnologies en cancérologie apporte un nouveau souffle dans le traitement des cancers. Les travaux réalisés par Olivier Tillement et ses collaborateurs ont permis de montrer que les nanoparticules de gadolinium (GdBN) sont capables d’augmenter d’une part la qualité d’imagerie par résonance magnétique (IRM) mais également d’augmenter les effets des rayonnements ionisants (IR) sur les tumeurs. Des études précliniques sur des tumeurs de glioblastome greffées sur des souris C57BL/6 ont permis de révéler la capacité de la combinaison GdBN+IR à favoriser une régression tumorale. Néanmoins, les processus de morts cellulaires impliqués sont partiellement connus. Nos résultats ont permis de démontrer que ce traitement produit un stress oxydatif généré par une NADPH oxydase. Ce stress oxydatif déclenche un arrêt de la prolifération des cellules qui dépend de la protéine p21 et qui déclenche un processus de sénescence cellulaire et le cannibalisme des cellules irradiées. Le cannibalisme cellulaire ainsi déclenché aboutit à l’élimination de cellules internalisées. Ainsi, l’ensemble de ces résultats nous a permis de révéler que la combinaison des GdBN et de l’irradiation contribue à l’élimination de cellules cancéreuses en déclenchant la sénescence des cellules irradiées ainsi qu’un mécanisme original de mort cellulaire, le cannibalisme cellulaire. / The nanotechnology aims to help in the cancer treatment. Olivier Tillement and his colleagues have demonstrated that the Gadolinium-Based Nanoparticle (GdBN) can improve Magnetic Resonance Imaging (MRI) and increase radiotherapy effects. Pre-clinical studies show that the combination of GdBN with ionizing radiation is associated with tumor regression. However, the molecular and cellular processes involved this biological effect remain to be elucidated. Our results show that the combination of GdBN with IR generates oxidative stress through NADPH oxidase-dependent mechanisms, leads to cellular senescence and induces the cannibalistic activity of irradiated cells. Altogether, these results reveal that the combination of GdBN with IR promotes the killing of irradiated cells through the induction of cellular senescence and cellular cannibalism.

Les nanoparticules sont de plus en plus présentes dans notre quotidien et leur présence dans les organismes vivants est aujourd’hui avérée. Aussi, dans un milieu biologique, des protéines recouvrent spontanément la surface des nanoparticules pour former une couronne de protéines. Suivant la composition de cette couronne, une nanoparticule acquiert une "identité biologique" spécifique qui peut conditionner sa biodistribution ainsi que son éventuelle toxicité.De nombreuses zones d’ombre persistent quant à la connaissance des mécanismes d’adsorption des protéines sur les nanoparticules. Deux caractéristiques physico-chimiques, peu abordées jusqu’à maintenant, ont été étudiées ici : la taille des protéines et la présence de modification post-traductionnelles. Aussi, du fait de leur forte utilisation, nous nous sommes concentrés sur les nanoparticules de silice (SiNPs).L’adsorption d’hémoprotéines, de nature similaire mais de tailles différentes, sur des SiNPs, elles-mêmes de tailles différentes, a été étudiée. Les isothermes d’adsorption et les titrations calorimétriques ont notamment montré qu’il existe une relation entre la taille des protéines et leur affinité pour une surface de silice. Des différences plus fines ont aussi pu être observées selon la taille des nanoparticules. Une analyse structurale des protéines adsorbées a également été effectuée par dichroïsme circulaire et diffusion de neutrons aux petits angles. Les hémoprotéines apparaissent comme des protéines très structurées qui sont peu affectées par l’adsorption. Cependant, bien que la structure quaternaire soit conservée, des modifications structurales sont observables.Des études faites en présence de mélanges de protéines (extraits de protéines de levure) ainsi que de peptides de synthèse ont également montré le rôle important de la diméthylation asymétrique de l’arginine sur l’interaction protéines/SiNPs. L’utilisation d’un panel de techniques expérimentales et de simulations a permis de comprendre le mécanisme responsable de la forte affinité de peptides contenant cette méthylation particulière. De façon plus générale, nos travaux suggèrent que les modifications post-traductionnelles peuvent influencer notablement les interactions de biomolécules avec des surfaces minérales. / Nanoparticles are ubiquitous in our environment and their presence inside our bodies is now established. Besides, in a biological medium, nanoparticles are spontaneously covered by proteins that form the so-called protein corona. Depending on the corona composition, a nanoparticle will possess a specific "biological identity" conditioning its biodistribution as well as its potential toxicity.Despite being highly studied, many aspects of the protein adsorption mechanisms remain unknown. Here we particularly focused on the influence of two physicochemical characteristics, which had rarely been addressed: protein size and post-translational modifications. Also, because of their intensive use, we worked on silica nanoparticles (SiNPs).We studied the adsorption of hemoproteins on SiNPs, both of them having different sizes. Adsorption isotherms and calorimetry studies showed a relationship between the protein size and its affinity towards silica surfaces. Finer differences could also be observed by varying the SiNPs size. Additionally, structural analyses of adsorbed proteins were performed using circular dichroism and small-angle neutron scattering. The adsorption of hemoproteins, which are well-structured proteins, seems to have little effects on their structure. However, even though the quaternary structure is maintained, structural modifications can be seen.Using yeast protein extracts and synthetic peptides, the major role of arginine asymmetric dimethylation on proteins/SiNPs interaction could be established. The use of experimental and simulation techniques allowed us to understand the mechanism responsible for the high affinity of peptides having this peculiar methylation. As a whole, this work suggests that post-translational modifications can influence considerably the interactions between biomolecules and mineral surfaces.

abstract: The applications utilizing nanoparticles have grown in both industrial and academic areas because of the very large surface area to volume ratios of these particles. One of the best ways to process and control these nanoparticles is fluidization. In this work, a new microjet and vibration assisted (MVA) fluidized bed system was developed in order to fluidize nanoparticles. The system was tested and the parameters optimized using two commercially available TiO2 nanoparticles: P25 and P90. The fluidization quality was assessed by determining the non-dimensional bed height as well as the non-dimensional pressure drop. The non-dimensional bed height for the nanosized TiO2 in the MVA system optimized at about 5 and 7 for P25 and P90 TiO2, respectively, at a resonance frequency of 50 Hz. The non-dimensional pressure drop was also determined and showed that the MVA system exhibited a lower minimum fluidization velocity for both of the TiO2 types as compared to fluidization that employed only vibration assistance. Additional experiments were performed with the MVA to characterize the synergistic effects of vibrational intensity and gas velocity on the TiO2 P25 and P90 fluidized bed heights. Mathematical relationships were developed to correlate vibrational intensity, gas velocity, and fluidized bed height in the MVA. The non-dimensional bed height in the MVA system is comparable to previously published P25 TiO2 fluidization work that employed an alcohol in order to minimize the electrostatic attractions within the bed. However, the MVA system achieved similar results without the addition of a chemical, thereby expanding the potential chemical reaction engineering and environmental remediation opportunities for fluidized nanoparticle systems. In order to aid future scaling up of the MVA process, the agglomerate size distribution in the MVA system was predicted by utilizing a force balance model coupled with a two-fluid model (TFM) simulation. The particle agglomerate size that was predicted using the computer simulation was validated with experimental data and found to be in good agreement. Lastly, in order to demonstrate the utility of the MVA system in an air revitalization application, the capture of CO2 was examined. CO2 breakthrough time and adsorption capacities were tested in the MVA system and compared to a vibrating fluidized bed (VFB) system. Experimental results showed that the improved fluidity in the MVA system enhanced CO2 adsorption capacity. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2019