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Preparation of a polymeric therapeutic targeting CD20 positive B-lymphomas and NK cells
Hejl, Maxmilián ; Vaněk, Ondřej (advisor) ; Bělonožníková, Kateřina (referee)
Malignant transformation of B-cells is manifested by a marked increase in the number of surface markers 20 (CD20, cluster of differentiation 20). In studying this trend, chimeric monoclonal antibodies targeting CD20 were introduced to induce apoptosis in B-lymphomas. Since the introduction of the first therapeutic monoclonal antibody rituximab, many others have been developed, with some still used to treat B-lymphomas today. Unfortunately, in many cases, resistance to these drugs is developing, and therefore the development of new types of therapeutics is still relevant. This work aims to develop a polymer-protein macromolecular conjugate capable of inducing apoptosis in CD20 positive leukemia cell lines. For this purpose, we work with biologically active vectors, so-called anti-CD20 nanobodies. This is a variable binding domain derived from the "heavy chain only" antibodies found in, e.g., llamas or camels. Compared to conventional antibodies, nanobodies are approximately ten times smaller, but their binding affinity for the antigen is not altered. For this reason, nanobodies are ideal candidates for attachment to a polymeric carrier, where poly-N-[2-(hydroxypropyl)methacrylamide] (pHPMA) was chosen in this work. The transpeptidase reaction catalyzed by recombinant sortase A, which recognizes and...
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Aliphatic polyester-based nanoparticles as drug delivery systems
Jäger, Alessandro ; Štěpánek, Petr (advisor) ; Sedláček, Jan (referee) ; Sikora, Antonín (referee)
Nanoparticles from biodegradable polymers are considered one of the most promising systems for biomedical application as drug delivery systems. Therefore, the synthesis and characterization of a new aliphatic biodegradable copolyester named PBS/PBDL (poly(butylene succinate-co- butylene dilinoleate)) intended to the application as drug delivery system is reported in the thesis. Surfactant-free biodegradable and narrowly distributed, nanosized spherical particles (RH < 60 nm) have been produced from the biodegradable material by applying a single-step nanoprecipitation protocol. The size of the generated polymer nanoparticles (PNPs) could be controlled by adjusting the polymer concentration, the choice of organic solvent, mixing different organic solvents or by changing temperature and ionic strength. By optimizing such parameters sub-100 nm uniform PNPs can be produced through this methodology including the advantage and ability to scale-up production. The nanoparticles structure was characterized in detail by employing a variety of scattering techniques and transmission electron microscopy (TEM). Combined static light scattering (SLS) and dynamic light scattering (DLS) measurements suggested that the nanoparticles comprise a porous core conferring them a non-compact characteristic. Their porosity...
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