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From Monomeric to Dendrimeric MRI Contrast Agents
Rudovský, Jakub ; Lukeš, Ivan (advisor) ; Botta, Mauro (referee) ; Peters, Joop (referee)
4, Conclueione To conclude, in my Thesis I found that ligands with phosphorus acid ped- a]11 alm substituting carboxylate in DOTA structure are endowéd with several Íavor- able features like a water residence liťetime optimal for a preparation of high- relaxivity covalent conjugates' Importantly, these promising p'óp.'ti.. were proved to persist even after the conjugation as was demonstrated ón u iy.."t.ical áitopic model compound for the first time. Imporlantly, the folrowing study of row- ge.nelatlon PAMAM conjugate proved that, unlike most oťthe published studies, trre rela:livity of these macromolecular systems ísnot exchang.-li.it"d. This has al. lowed meto investigate in detaíl the limiting effects on the iela;rivity of the internal ro^tation of the complex in the conjugates. In addition' I shown that tňe local mottons ofthe dendrimer backbone and ofthe conjugated complexes can be slowed down by a- formatíon of supramolecular adducts with cationic polyaminoacids. Also, I was able to quantitatively evaluate the effects of the local motíons and to effectively reduce them. As a result, the efficacy of these systems as relaxation agents is the highest so far reported for this class of compounds that can find a varieň of poten- tial biomedical/bioinorganic applications. For the close future, we plan in...
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Titaniun Dioxide - Phosphonate Assemblies as Medical Nanoprobes
Řehoř, Ivan ; Lukeš, Ivan (advisor) ; Lang, Kamil (referee) ; Peters, Joop (referee)
Titanium Dioxide - Phosphonate Assemblies as Medical Nanoprobes Ivan Řehoř PhD. Thesis Abstract: Multimodal imaging-therapeutic nanoprobe TiO2@RhdGd was prepared and successfully used for in- vitro and in-vivo cell tracking as well as for killing of cancer cells in-vitro. TiO2 nanoparticles, 12 nm in diameter, were used as a core for phosphonic acid modified functionalities, responsible for contrast in MRI and optical imaging. The phosphonic acid derivatives, used for surface modification, allows for grafting extraordinarily high loads of irreversibly adsorbed molecules of both types in one step. The prepared probe shows very high 1 H r1 relaxivity value as well as relaxivity density value, both crucial parameters for its use in MRI. The presence of fluorescent dye in its structure allows for its visualization by means of fluorescence microscopy. The applicability of the probe was studied, using three living systems - mesenchymal stem cells, cancer HeLa cells and T-lymphocytes. The probe did not exhibit toxicity in any of these systems and its long time storage in a lysosomal compartment was confirmed. Labeled cells were successfully visualized in-vitro by means of fluorescence microscopy and MRI. Consequent visualization of labeled cells in-vivo by means of fluorescence microscopy was also achieved....
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