Iskanje po katalogu digitalne knjižnice

Opis: Purpose: Phosphonates, like 3-AminoPropylphosphonic Acid (ApA), possess a great potential for the therapy of bone tumours, and their delivery via cellulose nanocrystals (CNCs) seems a promising approach for their increased efficacy in target tissues. However, the immunological effects of CNC-phosphonates have not been investigated thoroughly. The main aim was to examine how the modification of CNCs with phosphonate affects their immunomodulatory properties in human cells. Methods: Wood-based native (n) CNCs were modified via oxidation (ox-CNCs) and subsequent conjugation with ApA (ApA-CNCs). CNCs were characterised by atomic force microscopy (AFM) and nanoindentation. Cytotoxicity and immunomodulatory potential of CNCs were investigated in cultures of human peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MoDCs)/T cells co-cultures by monitoring phenotype, cytokines production, allostimulatory and Th/Treg polarisation capacity. Results: AFM showed an increase in CNCs’ thickens, elasticity modulus and hardness during the modification with ApA. When applied at non-toxic doses, nCNCs showed a tolerogenic potential upon internalisation by MoDCs, as judged by their increased capacity to up-regulate tolerogenic markers and induce regulatory T cells (Treg), especially when present during the differentiation of MoDCs. In contrast, ox- and ApA-CNCs induced oxidative stress and autophagy in MoDCs, which correlated with their stimulatory effect on the maturation of MoDCs, but also inhibition of MoDCs differentiation. ApA-CNC-treated MoDCs displayed the highest allostimulatory and Th1/CTL polarising activity in co-cultures with T cells. These effects of ApA-CNCs were mediated via GABA-B receptor-induced lowering of cAMP levels in MoDCs, and they could be blocked by GABA-B receptor inhibitor. Moreover, the Th1 polarising and allostimulatory capacity of MoDCs differentiated with ApA-CNC were largely preserved upon the maturation of MoDCs, whereas nCNC- and ox-CNC-differentiated MoDCs displayed an increased tolerogenic potential. Conclusion: The delivery of ApA via CNCs induces potent DC-mediated Th1 polarisation, which could be beneficial in their potential application in tumour therapy.
Ključne besede: cellulose nanocrystals, phosphonates, dendritic cells, regulatory T-cell subsets, immunomodulation, GABA-B receptor
Objavljeno v DKUM: 17.08.2023; Ogledov: 328; Prenosov: 21
Celotno besedilo (13,54 MB)
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Opis: The goal of this thesis is the structuring of cellulose nanocrystals using different organofunctional silane compounds and different cationic species to prepare highly functional materials with tailored properties. In addition different new aspects and approaches for the structural characterization of functionalised cellulose nanocrystals (CNC) functionalised with different organofunctionalalkoxysilanes as well as cationic species have been introduced. Cellulose nanocrystals (CNC) are prepared using three different acidic conditions to hydrolyse microcrystalline cellulose (MCC). The sulphuric acid hydrolysis introduces highly negative charged sulphate groups on the CNC. The aqueous nanocrystalline cellulose suspensions (aNCS) are analysed in terms of ζ-potential related to the pH and concentration to investigate the stability while dynamic light scattering (DLS) is used to investigate the size distribution. The hydrochloric acid hydrolysis in contrast only removes the amorphous regions but the so obtained CNC are less stabilized (decreased ζ-potential) and tend to agglomerate very fast. The use of the mixture of both acids (HCl and H2SO4) during the hydrolysis of MCC introduces less sulphate groups compared with the sulphuric acid hydrolysis. AFM investigations show that the shapes of the CNC are highly influenced by the hydrolysis conditions. While the shape of the H2SO4 hydrolysed CNC is rod like, while the shape of the other two CNC samples is more spherical in nature. One of the major topic in this work is the analysis of aNCS in aqueous solutions by small angle x-ray scattering (SAXS). The use of the generalized indirect Fourier transformation (GIFT) method allows the analysis of these systems and structural properties such as shape, size and surface charge of aNCS can be assessed. Using this kind of characterisation it can be seen that the shape of the H2SO4 hydrolysed CNC is definitely rod like while the other CNC sample can be described with spheres. In addition to the aNCS characterisation different substrates (Si-wafer, glass slides, polystyrene, etc.) are equipped with aNCS using a variety of different deposition methods (e.g. spin coating, solution casting, dip coating). The resulting films are studied in terms of morphology AFM, SARFUS and SEM. Sophisticated scattering techniques are employed for surface structural characterisation as grazing incidence small angel x-ray scattering. The determination of surface free energies allows conclusions about the hydrophilicity and hydrophobicity as well as the interaction capacity with different liquids. It can be seen that besides the hydrophilic nature of the CNC also hydrophobic interactions are present. The highly negative charged CNC sample which was prepared using sulphuric acid hydrolysis is found to be best suitable for the further hybridization with different organofunctional silanes and for the layer by layer approach (LBL) with different cationic species. The organofunctionalalkoxysilanes which were used in this study can be divided into three groups (e.g filler, surface functionalisation silanes, cross linking silanes). Depending on the nature of the organic residue the silanes are capable to introduce functionalities with enhanced hydrophobic and olephobic properties. The surface energies are investigated using contact angle method, while the surface energies are calculated using three different model approaches (OWRK, Wu, Acid-Base). The most increased hydrophobic and oleophobic properties were measured for trimethylfluorophenylsilantriol (PFTEOS). The morphology of the coated silanes is investigated using SAFRUS technique. It can be seen that nearly all silanes can be coated as homogeneous films onto different substrates (Si-wafer, SURFs, glass slides) with different methods (spin coating, solution casting). The macroscopic appearance of solution casted silanes is investigated using optical microscopy. The differences of the structural nature of the so obtained coatings and detaching films were investigated...
Ključne besede: Cellulose nanocrystals, sol-gel chemistry, organofunctionalalkoxysilanes, hybrid materials, small angle x-ray scattering, generalized indirect Fourier Transformation, quartz crystal microbalance dissipation, surface free energy, surface functionalisation, layer by layer
Objavljeno v DKUM: 28.11.2012; Ogledov: 2626; Prenosov: 173
Celotno besedilo (8,59 MB)