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Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Řezáčová, Martina (referee) ; Mosinger, Jiří (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of biochemical sciences Candidate Mgr. Miloslav Macháček Supervisor doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer. Photodynamic therapy (PDT) of cancer is non-invasive treatment modality for solid tumour treatment using three basic components - molecular oxygen, light and photosensitizer (PS). These elements are essentially non-toxic on their own, but in the combination they induce reactive oxygen species (ROS; singlet oxygen mainly) production, causing damage to cellular components and subsequent cell death. Type of cell demise is dependent mainly on the type of PS, length of irradiation and subcellular localization of the drug. Singlet oxygen is highly reactive and is capable of limited diffusion in biological environment. Apart from direct cytotoxic effect, vascular shutdown (oxygen and nutrition deprivation) and activation of immune system are involved in tumour eradication. Combination of effective compound with delivery system, conjugation with targeting substances or synthesis of highly effective non-aggregating water soluble compounds are the main pathways in design of modern PSs. In our...
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Nanofiber materials simultaneously photogenerating NO and 1O2 species; Reversible NO binding on boron-containing clusters
Dolanský, Jiří ; Mosinger, Jiří (advisor) ; Klán, Petr (referee)
This project is concerned with the preparation of electrospun polystyrene (PS) nanofiber materials with covalently bonded NO-photodonor and electrostatically attached tetracationic porphyrinoid photosensitizers. These photofunctional nanofiber materials exhibit effective simultaneous photogeneration of small antibacterial NO and O2(1 ∆g) species under irradiation with daylight creating an antibacterial surface and near surrounding. NO species can be also generated just by gentle heating. Nanofiber materials were analyzed with SEM, FTIR, emission and UV/vis spectroscopy and time-resolved emission and absorption spetroscopy. The antibacterial effect was tested on Escherichia coli. The dual antibacterial action, in combination with the nanoporous character of the material that detains pathogens like bacteria on its surface, is ideal for any application where a sterile environment is neces- sary. The known bimetallic cluster system [(PMe2Ph)4Pt2B10H10] that possesses the propen- sity to reversibly bind small gaseous molecules (O2, SO2, CO) was synthesized in good yields for NO reversible binding investigation. Seven new monometallic precursors (Pt, Pd and Ni) to new bimetallic species were succesfully synthesized with the aim of future study of NO reversible binding. All new compounds were purified by...
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Photooxidative and photodisinfective polymeric nanofabrics: The effect of oxygen permeability
Jesenská, Soňa ; Mosinger, Jiří (advisor) ; Lang, Kamil (referee)
The diploma thesis compares the photophysical, photooxidative and photocytotoxic properties of four polymer nanofabrics with encapsulated 5,10,15,20 - meso - tetraphenylporphyrin (TPP). The main focus of the work lies especially in the study of the effect of polymer oxygen permeability on the ability of nanofabrics to produce singlet oxygen and the utilization of nanofabrics for measurement of the polymer oxygen permeability and polymer oxygen diffusion coefficients. A possible application of nanofabrics in the framework of oxygen detection, photooxidation of substrates and photodesinfection has been studied as well.
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Polystyrene photoactive nanomaterials producing singlet oxygen
Henke, Petr ; Mosinger, Jiří (advisor) ; Dědic, Roman (referee) ; Kolářová, Hana (referee)
The increasing number of multidrug-resistant strains of bacteria call for alternatives to antibiotic therapy and, more generally, for the antimicrobial material as a component of prevention. Of particular interest is the photodynamic inactivation of bacteria and other pathogens caused by photogenerated singlet oxygen. This work is focused on the field of photoactive polymer nanofiber membranes and nanoparticles, generating singlet oxygen, suitable for medical applications. We prepared different types of photoactive modified polystyrene nanofiber membranes with encapsulated or externally bound porphyrin photosensitizers. These materials efficiently produce highly reactive and cytotoxic singlet oxygen capable of restricted diffusion into to the external environment. Our results demonstrate the crucial role of wettability for materials of this type with a short diffusion length of generated singlet oxygen, illustrate the effect of temperature and indicate their potential use as multifunctional materials. Due to their antimicrobial properties, these materials are suitable alternative to antibiotics and local antiseptics. With good breathability and short diffusion length of singlet oxygen good results can be expect in in vivo tests. From these nanofiber materials we also prepared photoactive extremely...
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Complexes of metals as potential anion receptors
Marečková, Vendula ; Vojtíšek, Pavel (advisor) ; Mosinger, Jiří (referee)
An important class of anion receptors are based on bimetallic complexes with phenols bearing an pendant arms in 2,6-positions. A ligand of this type, 2,6-bis[(N- methylpiperazine-1-yl)methyl]-4-formyl phenol (L1), was prepared using the Mannich reaction. An attempt to prepare a similar compound L2 yield only an oily product. The molecular structure of compound L1 was determinated by X-ray diffraction. Comparison of the L1 structure with similar ones from CCDC showed important influence of the intramolecular H-bond on pendant arms orientations in this type of compounds. Further synthetic exploitation of the aldehyde group (in the position 4) was tested by reaction with 4-nitroaniline. The Shiff base (L3) was obtained but only as an oily substance. Reactions of L1 with Cu(ii) and Zn(ii) perchlorate or acetate produce complexes; the compound [Cu2L1(OH)(OAc)(H2O)]ClO4 (K1) was obtained in a crystallic form. The interactions of anion-bimetallic complex receptor were discused from stereochemical point of view using the structural data from CCDC in the last part of this work.
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Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Řezáčová, Martina (referee) ; Mosinger, Jiří (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of biochemical sciences Candidate Mgr. Miloslav Macháček Supervisor doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer. Photodynamic therapy (PDT) of cancer is non-invasive treatment modality for solid tumour treatment using three basic components - molecular oxygen, light and photosensitizer (PS). These elements are essentially non-toxic on their own, but in the combination they induce reactive oxygen species (ROS; singlet oxygen mainly) production, causing damage to cellular components and subsequent cell death. Type of cell demise is dependent mainly on the type of PS, length of irradiation and subcellular localization of the drug. Singlet oxygen is highly reactive and is capable of limited diffusion in biological environment. Apart from direct cytotoxic effect, vascular shutdown (oxygen and nutrition deprivation) and activation of immune system are involved in tumour eradication. Combination of effective compound with delivery system, conjugation with targeting substances or synthesis of highly effective non-aggregating water soluble compounds are the main pathways in design of modern PSs. In our...
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The study of sulphonated polystyrene nanofabrics with encapsulated sensitizer
Hrdinková, Veronika ; Mosinger, Jiří (advisor) ; Vojtíšek, Pavel (referee)
The diploma thesis is dedicated to the exploitation of sulphonated polystyrene nanofibres as ion exchange nanomaterial. Ion exchange capacity of these nanomaterials has been determined by titration method and AAS. The effect of sulphonation on photophysical, photooxidative and photocytotoxic properties of sensitizer 5,10,15,20-meso- tetraphenylporphyrin (TPP) encapsulated in polystyrene nanofibres has been studied as well. Properties of TPP have been examined with time-resolved spectroscopy, photooxidation of uric acid as substrate and bactericidal tests on Escherichia coli DH5α with pGEM11Z plasmid. It has been discovered that following the sulphonation of the nanofabrics, the encapsulated sensitizer is partly present even in aggregation form. The polystyrene nanofabrics with encapsulated sensitizer keep its bactericidal efficiency also after sulphonation.
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