|
|
Anticancer drugs in forms of nanoparticles and mechanisms potentiating their anticancer efficiency
Meskařová, Veronika ; Indra, Radek (advisor) ; Bělonožníková, Kateřina (referee)
Cancer has been one of the most common diseases of civilization for centuries. In the 18th century, some cancers were described and the first treatments were proposed. Currently, oncosurgery, chemotherapy, radiotherapy, immunotherapy and hormonal treatment are used to treat cancer. At the same time, efforts are being made to find new anticancer drugs that target tumor cells more selectively. Recently, nanomedicine has also started to be used. This bachelor thesis deals with minimizing the binding of the amount of cytostatic ellipticine to the surface of the nanotransporter apoferritin and achieving higher encapsulation efficiency. Two types of apoferritins at different weight ratios to ellipticine were studied. It has been found that by finding a suitable weight ratio of the two molecules, binding can be minimized, and encapsulation efficiency can be increased. When working with commercial apoferritin, there was a higher encapsulation and a lower binding of ellipticine to the surface at the weight ratio of 1:10. In contrast, when working with recombinant apoferritin, the encapsulation is higher and ellipticine binding are lower at the lower ratio of 1: 2,5. Key words: oncological diseases, anticancer drugs, nanomedicine, cytostatic, nanotransporter, ellipticine, apoferritin [IN CZECH]
|
|
|
Novel Voltammetric DNA Biosensor for the Detection of the DNA Damage Caused by Oncological Drugs
Hrochová, Zuzana ; Vyskočil, Vlastimil (advisor) ; Zima, Jiří (referee)
This Bachelor Thesis is focused on the optimization of conditions for the use of a simple voltammetric DNA biosensor, based on a large-surface carbon film electrode (ls-CFE), for the detection of the DNA damage caused by oncological drugs. ls-CFE was used for its advantageous properties, such as its fast preparation, a simple mechanical renewal of the electrode surface, a good reproducibility of results, a simple chemical modification, and, last but not least, low preparation costs. A content of ethanol in the solution, in which the biosensor was incubated together with the damaging agent, was the main optimization parameter investigated in this Thesis. The contents of ethanol in the range from 0 to 50 % (v/v) of ethanol in 0.1 mol/l phosphate buffer of pH 7.15 (PBS) were tested. After the incubation of the biosensor, the measurements were performed using cyclic voltammetry (CV) in the presence of the redox indicator [Fe(CN)6]4-/3- in PBS. The optimum content of ethanol was found as 5 %. Afterwards, the DNA biosensor, which preparation was optimized in a previous Bachelor Thesis, was used for the detection of the DNA damage caused by model cytostatic agent - Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazol). Using the CV technique and the redox indicator [Fe(CN)6]4-/3- , the response of the biosensor to...
|
|
|
Assessment of in vitro antioxidant properties of medicinal and edible plant extracts
Tauchen, Jan ; Kokoška, Ladislav (advisor) ; Jaromír , Jaromír (referee)
Identification and characterization of plant-based products with antioxidant and anti-proliferative effects has received much interest over the past few years as possible therapeutic mean for treatment of diseases likely to be associated to oxidative stress (such as atherosclerosis, diabetes, and cancer). This study provides characterization of in vitro antioxidant and/or anti-proliferative potential and phytochemical profile of (i) 39 wine samples of underutilized Georgian grapevine cultivars, (ii) extracts of 22 samples of medicinal plants from Ethiopia and (iii) 23 samples of edible and medicinal plants from Peruvian Amazon. For this purpose, 2,2-diphenyl-1-picrylhydrazyl radical assay (DPPH), oxygen radical absorbance capacity (ORAC) assay, total phenolic content (TPC), and cell viability assay based on metabolization of tetrazolium bromide (MTT) to formazan, together with methods based on high performance liquid chromatography (HPLC-ultra violet/visible spectrometry and HPLC-tandem mass spectrometry) were used. Georgian red wines (particularly Saperavi cultivars) exhibited higher antioxidant capacity (average DPPH and ORAC values at 5.1 and = 10.6 g TE/L wine, respectively) in comparison to Central and West European cultivars [Pinot Noir (DPPH = 3.1 and ORAC = 9.4 g TE/L wine), Cabernet Sauvignon (DPPH = 3.0 and ORAC = 7.3 g TE/L wine) and Cabernet Moravia (DPPH = 2.0 and ORAC = 8.5 g TE/L wine)]. Georgian wines contained significantly greater concentrations of quercetin (between 14.44 and 1.07 ug/mL), kaempferol (between 1.68 and 0.03 ug/mL) and syringic acid (between 12.59 and 4.72 ug/mL), whereas possessed lower quantities of resveratrol (between 5.11 and 0.32 ug/mL) in comparison to Central and West European wines. Amongst edible and medicinal plants from Ethiopia and Peruvian Amazon, only Dodonaea angustifolia (IC50 for DPPH = 22.2 ug/mL, ORAC = 767.6 ug TE/mg extract; IC50 for Hep-G2 = 120.0 ug/mL), Rumex nepalensis (IC50 for DPPH = 5.7 ug/mL, ORAC = 1061.4 ug TE/mg extract; IC50 for Hep-G2 = 50.5 ug/mL), Inga edulis (DPPH and ORAC = 337.0 and 795.7 ug TE/mg extract; IC50 for Hep-G2 and HT-29 = 36.3 and 57.9 ug/mL) and Oenocarpus bataua (DPPH and ORAC = 903.8 and 1024.4 ug TE/mg extract; IC50 for Hep-G2 and HT-29 = 102.6 and 38.8 ug/mL) have demonstrated combinatory antioxidant/anti-proliferative efficacy. Selective anti-proliferative activity was observed for Verbascum sinaiticum (IC50 for Hep-G2 = 80.6 ug/mL) and Annona montana (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 ug/mL, respectively). Above-mentioned plant material showed only weak or non-toxic effects towards normal cell line. Despite the fact that extracts of Jasminum abyssinicum (IC50 for DPPH = 26.3 ug/mL, ORAC = 1023.7 ug TE/mg extract), Rumex nepalensis (IC50 for DPPH = 5.7 ug/mL, ORAC = 1061.4 ug TE/mg extract), Mauritia flexuosa (DPPH and ORAC = 1062.9 and 645.9 ug TE/mg extract), Myrciaria dubia (DPPH and ORAC = 641.9 and 642.6 ug TE/mg extract) and Theobroma grandiflorum (DPPH and ORAC = 714.8 and 821.9 ug TE/mg extract) have exhibited considerable antioxidant effect, these species were found to possess moderate to low anti-proliferative potential or have shown to be toxic to normal cells line. In all cases it was detected that phenolic compounds content correlated strongly with antioxidant activity, however weakly with anti-proliferative effect. Results suggest above-mentioned species as prospective materials for further development of novel plant-based agents effective against oxidative stress related diseases. However, it is necessary to perform further research which would be focused on detailed characterization of their chemical composition, pharmacological effects and toxicological safety, in order to verify their possible practical use.
|
guest ::
