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http://ciqa.repositorioinstitucional.mx/jspui/handle/1025/754| Hemagglutinin-derived peptides and their conjugation with block copolymers (Péptidos derivados de la hemaglutinina y su conjugación con copolímeros en bloques) | |
| CAROLINA VENTURA HUNTER | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| Doctorado en tecnología de polímeros | |
| This work investigates the conjugation process of polymer nanoparticles with peptides derived from the hemagglutinin (HA) protein of the influenza A virus. Two amphiphilic copolymer systems, one based on polyethylene glycol (PEG) and the other one on glycerol mono-methacrylate (GMMA) units, were considered for the formulation of the nanoparticles. An important part of this investigation was the synthesis of novel block copolymers with a precise macromolecular structure via the reversible addition– fragmentation chain transfer (RAFT) polymerization technique, the polymer structure was elucidated with the aid of proton nuclear magnetic resonance (1H-NMR) spectroscopy and size exclusion chromatography (SEC) techniques.
Copolymers based on the GMMA monomer are generally less explored systems in biomedical applications. Therefore, the copolymerization of GMMA with the comonomers N-succinimidyl methacrylate (NHSMA), N-isopropylacrylamide (NIPAM) and butyl acrylate (BuA) was investigated in more detail using high-throughput experimentation (HTE). The experimental results of this work enabled the determination of the reactivity ratios, the distribution of comonomer sequence lengths and the thermal properties (via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)) of the investigated comonomer systems. The selected conjugation pathway was via nucleophilic aminolysis of primary and secondary amines, which allowed the incorporation of the peptide units onto the copolymer chains. The obtained copolymer precursors and the peptide-copolymer conjugates tend to self-assemble in water due to their amphiphilic nature, enabling the formation of different nanostructures featuring morphologies such as micelles and vesicles as revealed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) investigations. The preparation of polymer nanoparticles conjugated with the peptides was further analyzed and quantified via fluorescence spectroscopy. Finally, the cytotoxicity of both the copolymer precursors and the peptide-copolymer conjugates as well as their internalization into Madin-Darby canine kidney (MDCK) cells were evaluated via presto blue assay and flow cytometry, respectively. | |
| 2024 | |
| Tesis de doctorado | |
| QUÍMICA | |
| Aparece en las colecciones: | Tesis de Doctorado |
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| Fichero | Descripción | Tamaño | Formato | |
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| Tesis DTP Carolina Ventura Hunter_.pdf | Tesis DTP Carolina Ventura Hunter | 8.05 MB | Adobe PDF | Visualizar/Abrir |