Amphiphilic block copolymers based on poly(ethylene glycol) (PEG) and poly(vinylidene fluoride) (PVDF) were synthesized by RAFT polymerization. The commercial poly(ethylene glycol) methyl ether (Me-PEG-OH, 20 Kg/mol) and difunctional polyethylene glycol (OH-PEG-OH, 20 Kg/mol) were used to synthesize diblock copolymers (Me-PEG-b-PVDF), and triblock copolymers (PVDF-b-PEG-b-PVDF) respectively. For the synthesis, the esterification reaction followed by the SN2 reaction was employed to make macro CTA (Me-PEG-XA, XA-PEG-XA, XA refers to the xanthate group). The macro CTAs were used further for VDF polymerization in dimethyl carbonate (DMC) inside the autoclave. Different molecular weights of the PVDF block (whether in the diblocks or the tribolcks) were obtained based on changes in the reaction time. The resulting block copolymers were molecularly characterized by FT-IR, 1H,19F-NMR, and SEC. The thermal properties were studied by DSC and TGA. Furthermore, the crystalline phase characterization was investigated by XRD and FT-IR. Being the obtained block copolymers are amphiphilic, their self-assembly was achieved by nanoprecipitation in DMF/water, and they were analyzed by DLS and TEM.

Self-assembly is a fundamental process in the field of nanotechnology, where molecules organize into complex structures spontaneously or induced by environmental factors. Peptides, short chains of amino acids, can self-assemble into many types of nanostructures. The self-assembly of peptides is governed by noncovalent interactions, including electrostatic interactions, hydrogen bonding, hydrophobic interactions, aromatic-aromatic interactions, and van der Waals forces. By varying the amino acid sequences and manipulating environmental parameters, these interactions can be modulated to obtain diverse supramolecular nanostructures, exhibiting a wide range of physical, chemical, and biological properties. Furthermore, the ability to control these properties opens up a world of possibilities in biomedical and biocatalytic applications. From drug delivery systems to enzyme mimics, as well as cancer treatments, the potential of these self-assembling peptides is vast and continues to be a vibrant area of research. Exploiting this potential, this dissertation delves into the design, synthesis, and investigation of self-assembling peptides for a range of applications. The introductory chapters of this document lay the groundwork, providing a comprehensive overview of self-assembly and its potential in biocatalytic and biomedical domains. The focus shifts in the later chapters to drug delivery applications, particularly in the delivery of hydrogen sulfide (H2S), and its implications in cardioprotection and cancer treatment. Finally, this document details an evaluation of self-assembled peptides in the context of biocatalysis using a combined experimental and computational approach. Chapter 3 discusses the design and synthesis of peptide-H2S donor conjugates (PHDCs) with an unusual adamantyl group. Several of PHDCs studied in this chapter self-assembled into novel nanocrescent structures observed under both conventional transmission microscopy (TEM) and cryogenic TEM (cryo-TEM). By varying the C-terminal amino acid with cationic, nonionic, or anionic amino acids, the PHDC morphologies remained unaffected, offering a robust peptide design for crescent-shaped supramolecular nanostructures. Chapter 4 discusses an extension of this project, introducing a cyclohexane in PHDCs instead of an adamantyl group. In this work, we designed and fabricated four constitutional isomeric PHDCs, which self-assembled into nanoribbons with different dimensions and large nanobelts. These morphologies exhibited varying cellular uptake and in vitro H2S release amounts, influencing their protective effects against oxidative stress induced by H2O2. With the knowledge of the impact of subtle changes in PHDC structures, Chapter 5 discusses our further design of three more PHDCs with the variation of side chain capping group, from an aromatic phenyl ring to a cyclohexane unit, to an aliphatic n-hexyl chain. In this chapter, we studied how changes in the hydrocarbon tail can influence the supramolecular nanostructures and their potential ability for colon cancer treatment. A final aspect of H2S delivery in Chapter 6 involves the creation of a stable PHDC with an extended H2S release profile. By integrating the H2S donor into a β-sheet forming peptide sequence with a Newkome-like poly(ethylene glycol) dendron, this PHDC self-assembles into spherical or fibril nanostructures with or without stirring. The H2S release was further studied by triggering release with various charged thiol molecules. Finally, another facet of this document focuses on three constitutional isomeric tetrapeptides containing a catalytic functional amino acid, His. Chapter 7 discusses these tetrapeptides, which self-assembled into nanocoils, nanotoroids, and nanoribbons based on the position of the His residue in the peptide sequence. Computational studies simulating the self-assembling process revealed the distribution of His residues and hydrophobic pockets, reminiscent of natural enzyme binding sites. A tight spatial distribution of His residues and hydrophobic pocket in nanocoils provided a picture for why this morphology exhibited the highest rate enhancement in catalyzing a model ester hydrolysis reaction. This study demonstrated how subtle molecular-level changes impact supramolecular nanostructures and catalytic efficiency. The final chapter details conclusions on all the research in this dissertation and discusses further directions of self-assembling peptides in the application of drug delivery and design of catalyst mimics. / Doctor of Philosophy / Self-assembly is a fascinating process in nanotechnology, where molecular building blocks come together to form complex structures. Peptides, which are short chains made up of amino acids, can play a crucial role in this process. They can organize themselves into various shapes due to different forces acting between their amino acid building blocks. By changing the arrangement of amino acids and adjusting the environment, scientists can create a wide range of nanoscale structures with unique properties from peptides. These self-assembling peptides have enormous potential in fields like medicine and catalysis. This dissertation describes how to design and make self-assembling peptides for various uses. Chapter 1 describes the general structure of the document, and Chapter 2 discusses the basics of self-assembly and how it can be applied in medicine and other areas. Chapters 3-6 focus on using self-assembling peptides to deliver hydrogen sulfide (H2S), a noxious gaseous molecule that is now recognized as a vital signaling molecule involved in various physiological processes. Several classes of peptide-H2S donor conjugates (PHDCs) are discussed in these chapters, including PHDCs that form nanoscale crescents, twisted ribbons, fibers, and other structures. These nanostructures show promise in protecting cells from harmful substances or can act as drugs in cancer treatment. We also investigate how different modifications affect their performance in biomedical applications. The final research chapter, Chapter 7, involves using self-assembling peptides as catalysts, molecules that speed up chemical reactions. By arranging the amino acids in different ways, peptides that form nanoscale coils, toroids, or ribbons-like structures were created. These different shapes influenced how well they catalyzed reactions. Computational modeling studies helped explain how small differences in molecular design led to big impacts on their catalytic abilities. The final chapter discloses conclusions on all the research in this dissertation and discusses the further directions of self-assembling peptides as medicines and catalysts.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24241号 / 農博第2520号 / 新制||農||1094(附属図書館) / 学位論文||R4||N5412(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 宮川 恒, 教授 三芳 秀人, 教授 森 直樹 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

The synthesis of a variety of novel functionalized polymers using living polymerization techniques to achieve functional and stimuli responsive coatings on silica surfaces are described. Since microscopic features on a surface influence the overall wetting properties of the surface, a systematic investigation of the influence of polymer architecture on the microscopic characteristics of the modified surfaces was studied using silane-functionalized linear and novel star-branched polystyrene (PS). Star-branched modifiers provide functional and relatively well-defined model systems for probing surface properties compared to ill-defined highly branched systems and synthetically challenging dendrimers. Using these simple star-shaped macromolecules it was shown that the topographies of the polymer-modified surfaces were indeed influenced by the polymer architecture. A model explaining the observed surface features was proposed. A living polymerization strategy was also used to synthesize centrally functionalized amphiphilic triblock copolymers. The amphiphilic copolymers exhibited stimuli responsive changes in surface hydrophobicity. In spite of multiple solvent exposures, the copolymer films remained stable on the surface indicating that the observed changes in surface properties were due to selective solvent induced reversible rearrangement of the copolymer blocks. The chemical composition of the copolymers was tailored in order to tune the response time of the surface anchored polymer chains. Thus, the polymer coatings were used to reversibly change the surface polarities in an on-demand fashion and could find possible applications as smart adhesives, sensors and reusable membrane devices. In contrast to the afore-mentioned covalent modification approach, which often leads to permanent modification of surfaces, renewable surfaces exhibiting "universal" adhesion properties were also obtained through non-covalent modification. By employing hydrogen bonding interactions between DNA bases, surfaces functionalized with adenine groups were found to reversibly associate with thymine-functionalized polymers. This study describing the solvato-reversible polymer coating was the first demonstration on silica surfaces. A systematic investigation of the influence of surface concentration of the multiple hydrogen bonding groups and their structure on the extent of polymer recognition by the modified surfaces is also discussed. / Ph. D.

Drought conditions and wildfires can induce soil water repellency. Precipitation shifts are expected to exacerbate drought and wildfire in regions such as the southeastern United States, making it critical to understand how repellency affects water exchange processes in soil. The objectives of this dissertation were to 1) quantify the water vapor sorption dynamics of two clay minerals in which water repellency was induced; 2) identify if and for how long wildfires in humid hardwood forests induce water repellency, 3) evaluate if organic carbon content and hydrophobic functional groups explain actual and potential soil water repellency; and 4) understand how vertical position (i.e., depth) of water repellent layers affect infiltration processes. To meet these objectives, a laboratory test was first conducted examining water vapor sorption processes in water-repellent clay minerals. Next, a field study occurred in two forests that experienced wildfires in late 2016: Mount Pleasant Wildfire Refuge, Virginia, and Chimney Rock State Park, North Carolina, United States. Measurements include water drop penetration time, soil water content, and tension infiltration. Complimentary laboratory tests quantified potential soil water repellency, soil organic carbon content and hydrophobic functional groups. Results showed that water repellency inhibited water vapor condensation because of altered mineral surface potentials and decreased surface areas. Burned hardwood forest soils presented water repellency for > 1 year, though laboratory measurements presented different trends than in situ measurements. Total organic carbon content and hydrophobic functional groups correlated with soil water repellency measured in the laboratory but not the field. Soil water content was lower in burned than unburned soils, and negatively correlated with water repellency. Water repellency in the surface layers significantly reduced relative water infiltration rates, whereas subsurface water repellency did not, and water repellency persisted longer in sites with surface compared to subsurface water repellency. Finally, while the wildfires increased the occurrence of water repellency, they did not alter the underlying relationship between relative infiltration and surface water repellency. Altogether, this study provided new insight into water repellency effects on water partitioning at soil-atmosphere interfaces, and presented evidence of soil and hydrological changes induced by wildfires in humid hardwood forests. / PHD / Rising temperatures and shifting precipitation patterns that result from global climate change have the potential to induce long-term droughts, which may induce soil water repellency, as can wildfires that become more prevalent and damaging. Water repellency can alter the physical, chemical, and hydraulic properties of soil. These alterations may drive soil erosional processes and increase the mobility of surface-bound pollutants with the potential to reduce water quality and degrade down-gradient aquatic ecosystems. Thus, it is critical to understand how water repellency affects water movement in and through soils. Despite several decades of research towards this topic, some critical questions still remain. For example, how does water repellent soil influence water characteristics in the vapor phase (which is increasingly important under drought conditions)? Do wildfires in humid hardwood forests cause soil water repellency? If so, how long does water repellency persist? Do water repellency measurements using field and laboratory techniques correspond to one another? How does the depth of water repellent soil layer(s) affect water movement? In order to solve this questions, several tests were conducted in both field and laboratory. The field experiments occurred within forested hillslopes that underwent varying degrees of burning during widespread wildfires that affected the Southeastern United States in late 2016. Choosing two forested locations, we measured actual water repellency, soil moisture, and infiltration in burned and unburned sites after wildfire, and took loose samples for laboratory tests. In the lab, we tested potential water repellency on air-dried soil samples, soil organic carbon content and hydrophobic substance percentage. We also conducted water vapor sorption experiments to quantify water vapor exchange in two types of water repellent minerals: kaolinite and montmorillonite. The results showed that water repellency can affect water exchange between the subsurface and the atmosphere, by both limiting water vapor sorption and reducing liquid water infiltration. Soil organic matter and composition correlate well with potential water repellency measured in the laboratory, though less so with actual water repellency measured in the field. Instead, soil water content provided a high and inverse correlation with actual water repellency. Finally, water infiltration rates were influenced by the vertical position (depth) of water repellent layers, with water repellency at the soil surface causing much reduced initial infiltration rates compared to water-repellent layers in the subsurface.

Ce travail de thèse concerne l’étude de dispersions de nanotubes de carbone (NTC) dans une matrice polymère afin d’obtenir des matériaux nanocomposites avec des propriétés améliorées. Dans la première partie, nous nous sommes intéressés à l’enrobage des NTC par des copolymères à blocs amphiphiles afin de faciliter la dispersion en solution aqueuse. L’influence de la structure chimique, de la composition et de la masse molaire des copolymères sur les propriétés a été étudiée. Dans une deuxième partie, l’incorporation des NTC dans une matrice polymère a été développée. Des procédés par voie aqueuse et par voie fondue ont été choisis afin de contrôler la répartition des NTC dans une matrice modèle de polyoxyde d’éthylène ainsi que dans des de polyéthylène ou de polyméthacrylate de méthyle. L’étude des propriétés physiques, notamment rhéologiques et électriques des nanocomposites à renfort de nanotubes a été réalisée. Ainsi les relations entre l’état des dispersions, la nature de l’enrobage et le mode d’élaboration des composites ont été établies. / This work is concerned with the study of carbon nanotubes (CNT) dispersions in a polymer matrix in order to obtain nanocomposite with unique properties. In the first part, we investigated the CNT wrapping by amphiphilic block copolymers to facilitate their suspension in aqueous solution. Based on the results, we could assess the effect on CNT dispersion quality of the molar mass of copolymers, the nature of the hydrophobic block and the length of hydrophilic block. In the second part, the incorporation of CNTs in polymer matrix was developed. Water or melt processing were chosen to control the distribution of CNTs in various polymer matrices (Polyethylene oxide, polyethylene and polymethyl methacrylate) through a prior wrapping of CNT. The studies of physical properties, including rheological and electrical properties, of nanocomposites were undertaken. Relationships between the state of dispersion, the nature of the coating and the method of preparation of composites were established.

Les polymères hydrosolubles sont utilisés dans diverses industries pour permettre la floculation, soit une séparation solide-liquide de particules présentes en suspension colloïdale. Afin de réduire les impacts environnementaux de l’exploitation des sables bitumineux en Alberta, l’industrie est à la recherche de nouveaux moyens et procédés pour traiter les résidus miniers permettant de séparer les matières solides et de récupérer l’eau. L’objectif des travaux présentés est d’améliorer la floculation, la densification et la déshydratation de ces résidus miniers aqueux par de nouveaux polymères synthétiques. Des homopolymères d’acrylamide de différentes masses molaires ont été synthétisés pour étudier l’influence de la masse molaire sur l’efficacité de floculation. Le taux initial de sédimentation (TIS) est le paramètre qui fut utilisé afin de comparer l’efficacité de floculation des différents polymères. Il a été possible de confirmer l’importance de la masse molaire sur l’efficacité de floculation et de déterminer une masse molaire minimale d’environ 6 MDa pour des polyacrylamides, afin d’obtenir l’efficacité de floculation maximale de suspensions colloïdales principalement composées de kaolin. Afin d’étudier l’effet des charges sur l’efficacité de floculation, des polymères anioniques et cationiques ont été synthétisés. Une série de copolymères d’acrylamide et d’acide acrylique ont été synthétisés comme polymères anioniques et deux séries de copolymères ont été synthétisés comme polymères cationiques, soit des copolymères d’acrylamide et de chlorure de diallyldiméthylammonium et des copolymères de 4-vinyl pyridine et de 1-méthyl-4-vinyl pyridinium. Il a été démontré que les charges anioniques des polymères avaient peu d’influence sur l’efficacité de floculation et que leur comportement en présence de sels était différent de ce que prévoyait la littérature. Il a aussi été démontré que les charges cationiques des polymères n’améliorent pas l’efficacité de floculation. Par la suite, des séries de copolymères amphiphiles, avec des monomères d’acrylamide, de N-alkylacrylamides et d’acrylonitrile, ont été synthétisés, pour étudier l’effet du caractère amphiphile sur la déshydratation des résidus miniers. Le pourcentage de déshydratation nette est le paramètre qui fut utilisé afin de comparer l’efficacité de déshydratation des différents polymères. Il a été possible de développer des copolymères amphiphiles qui améliorent l’efficacité de déshydratation par rapport à des homopolymères d’acrylamide. Il ne fut pas possible de déterminer une tendance entre la balance hydrophile/hydrophobe des copolymères amphiphiles et l’efficacité de déshydratation. / Water soluble polymers are extensively used in industry to achieve solid-liquid separations of particles in colloidal suspensions. In a way to reduce the environmental footprint of the mining exploitation, the oil sands industry is searching for new methods to treat tailings resulting from the extraction processes, by separating the solids and recycling the water. The objective of this work is to improve the flocculation and dewatering efficiency of the water-based tailings through the use of new synthetic polymers. Acrylamide homopolymers of different molecular weights were synthetized to study the effect of molecular weight on flocculation efficiency. Initial settling rate (ISR) was the parameter measured to characterize and compare the flocculation efficiencies. The important effect of polymer molecular weight on the flocculation efficiency was confirmed. The minimum molecular weight of polyacrylamide for optimal flocculation efficiency of kaolin colloidal suspensions has been determined to be around 6.8 MDa. To study the effect of charge on flocculation efficiency, anionic and cationic copolymers were synthetized. Copolymers of acrylamide and acrylic acid have been synthetized to study the effect of anionic charge, whereas copolymers of acrylamide and diallyldimethylammonium chloride and copolymers of 4-vinyl pyridine and 1-methyl-4-vinyl pyridinium have been synthetized to study the effect of cationic charge. Anionic copolymers have shown limited effect on the flocculation efficiency and their behaviour in salt solution was revealed to be different than expected from the literature. Cationic copolymers have shown no improvement in the flocculation efficiency. Amphiphilic copolymers were synthetized with acrylamide, N-alkylacrylamides and acrylonitrile monomers to study the effect of amphiphilicity on the dewatering efficiency of tailings. The net water release parameter was measured to compare the dewatering efficiency of the polymers. Amphiphilic copolymers that improve tailings’ dewatering, compared to polyacrylamide, were developed. Thus far, it was not possible to define a trend between hydrophilic/hydrophobic balance and dewatering efficiency of the copolymers.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Les poly (3-hydroxyalcanoates) (PHAs) sont des polyesters aliphatiques produits et accumulés par des bactéries en tant que réserve de carbone et d'énergie. Ils sont constitués d'unités β-hydroxyesters et possèdent des chaînes latérales de longueur variable, pouvant être fonctionnalisées. Ils possèdent des propriétés de biodégradabilité et de biocompatibilité; ceci leur confère de vastes possibilités d'utilisation dans le domaine biomédical, notamment pour la mise au point de systèmes de libération contrôlée de principes actifs. Dans cette optique, nous nous sommes intéressés à la synthèse de copolymères amphiphiles de différentes architectures à base de PHAs, ainsi qu'à l'étude de leurs propriétés d'auto-association en milieu aqueux. Une méthode simple et efficace permettant le greffage d'oligomères de poly (éthylène glycol) (PEG) a tout d'abord été mise au point grâce à l'utilisation de la chimie « click ». Une série de copolymères diblocs bien définis PHA-b-PEG a ainsi pu être synthétisée par cycloaddition de Huisgen catalysée par le cuivre (CuAAC). Les copolymères diblocs à base de PHAs à moyennes chaînes latérales (PHA-mcl) ont montré leur capacité à s'auto-associer en milieu aqueux et à former des micelles monodisperses présentant une concentration micellaire critique très faible. Par la suite des copolymères de type greffés PHOU-g-PEG ont été synthétisés par addition thiol-ène. Les analyses par cryo microscopie électronique à transmission (cryo-TEM) ont montré que dans ce cas les copolymères s'auto-associaient en structures vésiculaires, ou polymersomes. Enfin, la synthèse de copolymères amphiphiles greffés porteurs de chaînes perfluorées PHOU-g-(F;PEG) a permis l'obtention de structures auto-associées plus complexes. Le cryo-TEM a en effet révélé la formation de micelles multicompartimentées, c'est à dire possédant un coeur présentant une séparation de phase entre les domaines hydrophobes et les domaines fluorés. Des tests biologiques préliminaires ont montré la cytocompatibilité de ces micelles / Poly (3-hydroxyalkanoates) are natural aliphatic polyesters produced and accumulated by many bacteria as carbon and energy supply. They consist of β-hydroxy ester units, with pendant side chains of different lengths that can be functionalized. Thanks to their biodegradability and biocompatibility, they are promising polymers for biomedical applications, especially for controlled drug delivery systems. In this context, we aimed to synthesize PHA-based amphiphilic copolymers with different molecular architectures, and to study their self-assembly in water. First, a simple and straightforward method using click chemistry has been used to graft poly(ethylene glycol) (PEG) oligomers. A series of well-defined diblock copolymers PHA-b-PEG has thus been synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Medium chain length PHA-based diblock copolymers have shown their ability to self-assemble into stable micelles having very low critical micelle concentrations. Afterwards, amphiphilic graft copolymers PHOU-g-PEG have been synthesized using thiol-ene addition. In this case, cryo-electron microscopy (cryo-TEM) analysis revealed that graft copolymers self-assembled into vesicular morphologies, i.e. in polymersomes. Finally, the synthesis of amphiphilic graft copolymers bearing perfluorinated chains PHOU-g-(F;PEG) was performed. After aqueous self-assembly, cryo-TEM shown the formation of multicompartment micelles, i.e. with a core displaying segregated hydrophobic and fluorophilic domains. Moreover, these multicompartment micelles have shown their cytocompatibility

Esse trabalho apresenta resultados de modificações estruturais, caracterizações e aplicações de derivados de quitosana como carreadores de fármacos. Derivados anfifílicos de quitosana, contendo grupos hidrofílicos e grupos hidrofóbicos, foram caracterizados por técnicas de espectroscopia de ressonância magnética nuclear (RMN1H), espectroscopia na região do infravermelho (IV), espectroscopia na região do UV-Vis, técnicas termoanalíticas (termogravimetria (TGA), termogravimetria derivada (DTG), análise térmica diferencial (DTA) e calorimetria exploratória diferencial (DSC)), fluorescência no estado estacionário, espalhamento dinâmico de luz (DLS) e microscopia eletrônica de transmissão (MET). Os resultados de caracterização mostraram que as sínteses propostas foram realizadas com sucesso. A determinação da concentração de agregação crítica (CAC) e os estudos de DLS e MET confirmam que os derivados se auto-organizam em solução aquosa formando agregados com diâmetros variando entre 230 a 500 nm. Esses valores, associados aos potenciais zeta obtidos (+14,1 mV a +44,8 mV), demonstram que os agregados são estáveis em solução, característica fundamental para aplicação no transporte de fármacos. A capacidade de encapsulamento do fármaco quercetina por esses derivados foi avaliada por estudos de incorporação utilizando a espectroscopia UV-Vis. Os resultados obtidos demonstraram que o comportamento dos derivados depende de parâmetros como o grau de hidrofilicidade e grupo hidrofílico, grau de hidrofobicidade e pH do meio de encapsulamento, possibilitando controlar a quantidade de fármaco contida nos carreadores. A atividade biológica dos agregados formados pelos derivados de quitosana foi testada em células de adenocarcinoma de mama (MCF-7) e os resultados indicaram baixa toxicidade dos carreadores, além de potencialização do efeito terapêutico do fármaco. Estudos de microscopia confocal de varredura a laser evidenciaram que agregados marcados com proteína verde fluorescente com afinidade por quitosana (CAP-sfGFP) foram internalizados pelas células MCF-7. Resultados de hemocompatibilidade indicaram que os polímeros apresentam baixa destruição de glóbulos vermelhos do sangue e liberação de hemoglobina. Portanto, esses derivados possuem características adequadas para aplicação no transporte e liberação controlada de fármacos. / This thesis presents results of structural modifications, characterizations and applications of chitosan derivatives as drug carriers. Amphiphilic derivatives of chitosan containing hydrophilic and hydrophobic groups were characterized by nuclear magnetic resonance spectroscopy (RMN1H), infrared spectroscopy (IV), uv-vis spectroscopy, thermoanalytical techniques (thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA) and differential exploratory calorimetry (DSC)), fluorescence, dynamic light scattering (DLS) and transmission electron microscopy (MET). The characterization results showed that the proposed syntheses were successfully performed. The critical aggregation concentration (CAC), DLS and MET studies confirmed that the derivatives self-assembled in aqueous solution forming aggregates with diameters ranging from 230 to 500 nm. These values, associated with zeta potentials (+14.1 mV to +44.8 mV), demonstrate that the aggregates were stable in solution. The ability to encapsulate quercetin by these derivatives was assessed by incorporation studies using UV-Vis spectroscopy. The results showed that the behavior of the derivatives depends on parameters such as the degree of hydrophilicity and hydrophilic groups, degree of hydrophobicity and pH of the encapsulation medium. The biological activity of the aggregates formed by the chitosan derivatives was tested in breast cancer cells (MCF-7) and the results indicated low toxicity of the carriers, in addition to improving the therapeutic effect of the drug. Confocal laser scanning microscopy studies showed that aggregates stained with chitosan-affinity protein (CAP-sfGFP) were internalized by MCF-7 cells. Hemolysis assays showed good hemocompatibility of chitosan derivatives. Therefore, the derivatives have suitable characteristics for application as drug delivery systems.