National Repository of Grey Literature 3 records found  Search took 0.00 seconds. 
In silico design and validation of conotoxin-based peptides for neuroblastoma nanotherapy
Mokrý, Michal ; Gumulec, Jaromír (referee) ; Heger, Zbyněk (advisor)
Práca sa zaoberá in silico dizajnom a validáciou peptidov založených na konotoxíne - MrIA, izolovaného z morských slimákov druhu Conus marmoreus a možnosti využitia týchto peptidov v liečbe neuroblastómu pomocou cielenia norepinefrínového transportéru. Päť peptidov založených na tomto konotoxíne bolo simulovaných pomocou simulácii molekulárnej dynamiky, ich trajektórie boli analyzované pre zistenie vlastností týchto peptidov. Dva homologické modely ľudského norepinefrínového transportéru boli vytvorené pre analýzu väzobných vlastností peptidov založených na konotoxíne ku norepinefrínovému transportéru. Peptidy boli následne syntetizované a použité na pokrytie apoferitínových nanočastíc s elipticínom uväzneným vnútri apoferitínu. Vytvorené peptidy a nanočastice boli ďalej skúmané pre objasnenie ich fyzikálo-chemických vlastností. Interakcie a cytotoxicita boli skúmané aplokáciou nanočastíc na bunky neuroblastómu a epitelu. Z in silico a in vitro analýz vyšiel YKL-6 peptid ako najlepší kandidát na ďalší výskum.
In silico design and validation of conotoxin-based peptides for neuroblastoma nanotherapy
Mokrý, Michal ; Gumulec, Jaromír (referee) ; Heger, Zbyněk (advisor)
Práca sa zaoberá in silico dizajnom a validáciou peptidov založených na konotoxíne - MrIA, izolovaného z morských slimákov druhu Conus marmoreus a možnosti využitia týchto peptidov v liečbe neuroblastómu pomocou cielenia norepinefrínového transportéru. Päť peptidov založených na tomto konotoxíne bolo simulovaných pomocou simulácii molekulárnej dynamiky, ich trajektórie boli analyzované pre zistenie vlastností týchto peptidov. Dva homologické modely ľudského norepinefrínového transportéru boli vytvorené pre analýzu väzobných vlastností peptidov založených na konotoxíne ku norepinefrínovému transportéru. Peptidy boli následne syntetizované a použité na pokrytie apoferitínových nanočastíc s elipticínom uväzneným vnútri apoferitínu. Vytvorené peptidy a nanočastice boli ďalej skúmané pre objasnenie ich fyzikálo-chemických vlastností. Interakcie a cytotoxicita boli skúmané aplokáciou nanočastíc na bunky neuroblastómu a epitelu. Z in silico a in vitro analýz vyšiel YKL-6 peptid ako najlepší kandidát na ďalší výskum.
Využití funkčních potravin v terapii nádorových onemocnění
Vašíčková, Kateřina
This diploma thesis with the name „Use of Functional Food in Cancer Therapy“ is focused on the study of the possibility of using nutraceuticals of functional food in cancer therapy. Literary part of this work deals with the topic of functional food and their positive effects on human body, especially in prevention and treatment of various type of diseases. One of the main topic is cancer and its treatment options. These days, research using nutraceuticals as a supplementary treatment or monotherapy modality of cancer is often the subject of research. In this work, the effect of nutraceutical curcumin, whose antitumor effects were tested in vitro in both monotherapy and supplementary breast cancer treatment, were investigated. As a supplementary treatment, curcumin was tested in synergy with the cytostatic doxorubicin. Biologically active molecules have been encapsulated into a cavity of protein nanocarrier apoferritin, which has been promoted to support molecule´s therapeutic effects while protecting non-transformed breast cells. The encapsulation efficiency was about 68–72 % for all applied molecules. Stability of encapsulated curcumin and doxorubicin complexes stored in aqueous medium at 4 °C and 20 °C for 48 hours was determined by monitoring the change in optical properties, the size and surface ζ-potential of the nanoparticles or premature drug release from the nanotransporter. In addition, a colloidal stability test have been confirmed the increased protection of biologically active molecules by the process of direct encapsulation. In solutions simulating the internal environment of the organism (blood plasma, cytoplasm, endosomes), the amount of the released molecules from the apoferritin cavity was monitored at 37 °C for 48 hours. The colloidal stability test determined the blood plasma behavior for 48 hours. The toxicity of the tested complexes against the tumor cell lines MDA-MB-231 and MDA-MB-468 was determined by several cell experiments. The HBL-100 cell line was consider as a control non-transformed cells. The research of this diploma thesis determined the oxidative stress of cell lines induced by prepared com-plexes and the rate of internalization of these formulations into cells. Biocompatibility was determined by monitoring protein corona formation on the surface of nanoparticles, activation of C3 complement component, genotoxic effects on healthy breast cell lines and hemolysis of erythrocytes in human blood.

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