čas: 19.4.2021 05:00:02
Obnovit | RAW
Institute of Macromolecular Chemistry CAS
List of available PhD theses
Advanced macromolecular systems for the genetic vaccine delivery
Active immunization of the body using vaccines has gained an indispensable role in the prophylaxis of various types of infectious diseases. In terms of safety and efficacy, vaccines based on modified viral RNA or DNA (so-called genetic vaccines), encoding protein antigens on the surface of microbial pathogens (viruses or bacteria) or tumor cells responsible for eliciting an immune response, are of great promise to the future. However, a limiting factor for genetic vaccines is the low stability of nucleic acids in the blood and the moderate immunogenicity. An elegant solution is the use of a macromolecular systems based on synthetic polycations, which form electrostatic complexes with nucleic acids protecting them from degradation. In addition, polycation allows the attachment of an immunostimulatory molecule (so-called adjuvant) to its structure, which significantly increases the immune response towards the antigen. The synthesis and physicochemical characterization of methacrylamide-based cationic polymers and their ability to complex, stabilize and release nucleic acids at various physiological conditions will be studied. The conjugation of imidazoquinoline-based adjuvants with polycations will also be addressed. Biological testing of macromolecular genetic vaccines will be realized in a cooperation with the foreign partner.
Bioactive coatings promoting spontaneous endothelialization of vascular vessel grafts
The surface of biomaterials that are in long-term contact with blood (e.g., vascular prostheses, stents) triggers inflammatory processes of the organism leading to activation of the coagulation cascade and formation of thrombi, and to a subsequent graft failure. The aim of this work is the development of coatings that would suppress activation of the coagulation cascade and immune response of the organism, while actively encouraging the formation of endothelium on the surface of vascular prostheses after their implantation. One approach will be based on coating the internal surface of a synthetic and decellularized vessel with a fibrin network that will be modified by bioactive molecules such as heparin, growth factors, oligosaccharides, and other bioreceptors specifically promoting the adhesion of progenitor endothelial cells. An alternative approach will be based on suppressing the unwanted body reactions by means of so-called polymer brushes and their subsequent functionalization by the above-mentioned biomolecules. We assume that, after implantation, heparin will suppresses the coagulation cascade, while the other bioactive molecules will promote endothelization of the graft by capturing progenitor endothelial cells from blood.
Biodegradable polymer systems for medical applications
Biodegradable and biocompatible polymer systems show numerous applications in both human and veterinary medicine. We have recently developed and patented multiphase polymer systems based on thermoplasticized starch (TPS), polycaprolactone (PCL), titanium dioxide based nanoparticles (TiX) and antibiotics (ATB). Morphology and properties of these systems can be adjusted by their composition and targeted phase structure modification during the processing. TPS/PCL/ATB systems can be employed in treatment of strong local infections such as osteomyelitis. The project comprises preparation of the above systems (by melt mixing), optimization of their phase structure (targeted modification of processing conditions), characterization of their morphology (electron microscopy), properties (macro- and micromechanical properties), and participation in medical tests in collaboration with local hospital (FN Motol; treatment of local infects, biodegradability).
MOF and COF materials for Li-ion batteries: synthesis, structure and ionic dynamics.
The development of hybrid and full electric vehicles raises the demand for electrical energy generation and storage devices. Well-defined porous architecture that allow Li-ions to be stored and reversibly inserted/extracted, predetermines MOF and COF materials to be explored as electrode as well as electrolyte materials for Li-batteries (LiBs). The aim of this PhD project is to develop a novel class of these framework materials modified by metallacarborane compounds and find a suitable polymer matrix allowing to reach optimal flexibility and ionic conductivity in absence of solvent molecules. The project work includes preparation of the composite materials and their detailed physicochemical and structural characterization.
NMR crystallography of active pharmaceutical ingredients
In the NMR Department of the IMC there is an urgent need for lowering the computational cost and at the same time increasing the robustness of the crystal structure prediction-based NMR crystallography approach to structural elucidation of powders and other forms of molecular solids. The project aims at analyses of the crystal-symmetry elements together with other geometry parameters in order to find and implement structural constraints and/or restraints into our NMR crystallography protocol. In addition, extensive database searches of the investigated structural motifs will be used.
Nanotherapeutics based on antimicrobial peptides for multiresistance bacteria species treatment
The work will be focused on the study of biodegradable polymeric nanomaterials carrying antimicrobial peptides. The studied nanomaterials will have a linear, branched or star-like structure composed from hydrophilic or amphiphilic copolymers containing stimuli-sensitive linkers. The aim of this work will be to develop an effective nanotherapeutic for the treatment of infections caused by resistant bacteria. The biological activity of these polymeric nanomaterials will be studied in dependence on the detailed structure of the whole system. The student will extend his/her knowledge in the area of preparation of mentioned nanomaterials, in vitro biochemical and biological testing and in vivo biological characterization of nanomaterials. The applicant's knowledge and experience in organic and / or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
New concept of enhancing targeting of polymer conjugates for drug delivery to brain
The aim of the Ph.D. thesis is to develop a conceptually new system for inhibition of glutamate carboxypeptidase II (GCP II) in brain as a treatment tool for suppressing glutamate toxicity and subsequent neuroinflammation-caused secondary damage after ischemic, hemorrhagic or traumatic brain injuries (which typically damage brain and spinal cord more than the primary injury and are the reason why neural damage often gets worse within few days after first occurrence of symptoms). The delivery system will modify the unfavorably hydrophilic properties of the GCP II inhibitors, which are normally unable to cross the blood-brain barrier (BBB). The delivery system will also enhance inhibitor potency by forming multivalent physically self-assembled („molecular toolbox“) biocompatible polymer-coated solid lipid nanoparticles. The inhibitor-containing nanoparticles will decompose after crossing the BBB by apolipoprotein E-mediated transfer and the polymer-bound inhibitor will become reversibly membrane-anchored in the proximity of the membrane-bound GCP II. This membrane anchoring is expected to be a generally applicable concept for targeting also enzymes or receptors other than GCP II.
Polymer-bound reactive oxygen species precursors for cancer therapy
Radiation therapy applies ionization radiation to cancer tissue to elicit the reactive oxygen species (ROS) production to kill the cancer cells. The radiation treatment can be boosted by application of radiosensitizers. The aim of this thesis is to prepare a polymer material that is able to deliver artificial ROS into the cancer cells or deliver precursors that will trigger the ROS generation at the place of action. Moreover, specific hypoxic markers can be utilized for active targeting to hypoxic tumor tissue. The student will design and prepare polymer systems which will be releasing ROS as: superoxide, peroxides or singlet oxygen in desired cancer site. The project is highly multidisciplinary, it includes polymer and organic syntheses, characterization techniques such as FTIR, 1-H 13-C NMR, SEC, DLS, SAXS and SANS. Moreover, the student can participate on biological studies which will be performed on collaborating workplace. If the student is interested in, it is possible to make part of the study at collaborating workplace in France within the program “double degree PhD”, the deadline is February 14, 2020 (see https://studium.ifp.cz/cz/doktorandi/barrande-fellowship-program/ ). If you are interested in this option, please contact the supervisor as soon as possible.
Polymeric nanomaterials for neoadjuvant multimodal therapy of advanced neoplastic diseases
The main aim of this work will be the development of new multi-component biocompatible and non-immunogenic polymer-based nanotherapeutics and nanodiagnostics adapted for multimodal advanced therapy of neoplastic diseases. The dissertation will be based on the preparation of new polymeric nanomaterials that will allow the controlled delivery of active therapeutic agents or tumor visualization for fluorescently navigated surgery. These nanomaterials will serve as a tool for multimodal neoadjuvant therapy based on sequential administration of chemotherapy and immunotherapy in combination with fluorescently navigated surgery. The work will focus on tailor-made solutions using covalent binding of active molecules with several functions: targeted transport of active molecules, their protection during transport against degradation and controlled release based on site-specific stimuli. The thesis will consist in the design, synthesis and study of physico-chemical and biological properties of polymeric materials. The applicant's knowledge and experience in organic or macromolecular chemistry is an advantage, along with the desire to learn new things in other fields, such as biochemistry. The work assumes close cooperation with cooperating biological teams in the Czech Republic and abroad.
Preparation of stimuli-responsive polymer nanomedicines using microfluidic nanoprecipitation – the in vitro and in vivo performance under simulated physiological conditions
Nanomedicines gain much more relevance in biomedical applications if they are tailored to be degradable in response to certain external stimuli. Such stimulus may be enzymatic removal of protecting groups, a pH change, light or the presence of reactive oxygen species (ROS) in cancer. Herein, imbalances on the cells micro-environment (pH changes, ROS production) will be explored for the synthesis of stimuli-responsive polymers and block copolymers. Inspired by the ease and effectiveness of the self-assembly of amphiphilic block copolymers in solution, several polymer nanomedicines, i.e., micelles, nanoparticles and vesicles will be designed to display tunable stimuli degradation in the presence of physiologically relevant changes in pH, temperature or ROS concentrations and will be prepared by microfluidic nanoprecipitation. This technique allows us the production of uniform particles with controllable size, shape and surface chemistry in a reproducible manner. The produced polymer self-assemblies will be characterized using standard scattering techniques (DSL/SLS/ELS, SAXS and SANS) and by microscopy. The effectiveness of the polymer nanosystems will be evaluated in in vitro and in in vivo models simulating the physiological balanced and imbalanced of the microenvironment.
Self-cleaning anti-biofilm polymer surfaces
The formation of bacterial biofilms is a one of the major issues in the current biomedical research. In the body, such biofilms are created on the surface of the medical devices, e.g., joint prostheses or heart valves, where they cause inflammation and chronic infections. The aim of this Ph.D. project is to develop a novel class of smart self-cleaning anti-biofilm polymer surfaces, based on poly(2-alkyl-2-oxazoline)s, that are both anti-fouling and able to catalytically prevent the biofilm formation in the very long-term period. The project work includes polymer synthesis, the surfaces preparation and the study of their physicochemical properties. Moreover, the selected surfaces will be subjected to comprehensive in vitro and in vivo testing in the collaboration with biologists.
Stimuli-responsive supramolecular polymer systems for biomedical applications
Self-assembly of (macro)molecules is of crucial importance in the architecture of living organisms. Supramolecular systems have their key properties critically dependent on self-assembly and find use in the area of biomedical applications especially if they are able to reversibly react to external stimuli (changes in pH, light, redox potential, ultrasound, temperature, concentration of certain substances). The doctoral thesis will be based on chemical and/or physicochemical preparation and study of self-assembly of such multi-stimuli-responsive nanoparticles with external environment (pH, redox potential and temperature responsiveness); the exact topic will take into account the student´s interests. The studied nanoparticles and injectable depot systems will be designed for diagnostics and personalized immunoradiotherapy and immunochemotherapy of cancer and autoimmune diseases. Optimized nanoparticles will be then provided to collaborating biological workplaces for in vivo testing.