Topics of diploma/bachelor thesis - Polymer and Colloid Immunotherapeutics
1) Synthetic macromolecular systems for targeted gene delivery
The thesis will focus on the development of non-viral vectors for targeted gene delivery, based on electrostatic complexes of synthetic copolymers with nucleic acids (NAs). These polymers will comprise hydrolytically degradable cationic blocks capable of compacting NAs into nanoparticles, and hydrophilic, electrically neutral blocks ensuring the colloidal and biological stability of the resulting complexes. The main emphasis will be placed on the synthesis and physicochemical characterization of diblock copolymers, their ability to complex and release NAs in response to the pH of the biological environment, and their transfection efficiency in selected cell lines. The project will employ modern synthetic and bioconjugation techniques, together with advanced physicochemical methods (NMR, SEC, DLS, electrophoresis, etc.) and work with cell cultures.
Contact person: Ing. Richard Laga, Ph.D., e-mail: laga, tel.: 325 873 806
Place of work: Institute of Macromolecular Chemistry CAS, BIOCEV, Průmyslová 595, 252 50 Vestec
2) Manganese oxide-based nanoparticles for applications in immunology and diagnostic imaging
Due to their physicochemical characteristics, manganese oxide nanoparticles (MONP) offer potential for use in MRI imaging and immunology. The project will primarily focus on the stabilization and surface modification of MONP using synthetic biocompatible (co)polymers with variable primary and secondary structures. The work will include morphological characterization using TEM, hydrodynamic characteristics using DLS methods, and structural characteristics using spectroscopic and chromatographic methods. Polymers for MONP surface treatment will be prepared using pseudo-living radical and oxidative polymerization methods so that the subsequent surface treatment ensures the desired behavior during MRI imaging and contact with components of the immune system. In the final phase of the project, the behavior of these MONPs in biological environments such as culture media and serum proteins, or possibly cell cultures, will be studied.
Contact person Ing. Michal Babič, Ph.D., e-mail: babic
Place of work: Institute of Macromolecular Chemistry CAS, areál BIOCEV, Průmyslová 595, 252 50 Vestec
3) Methacrylamide and acrylamide copolymers sensitive to external stimuli: advanced drug delivery systems and diagnostics
Polymeric micelles and nanoparticles are studied in the field of drug delivery and targeted drug release, especially in anticancer therapy. Thanks to their size (20-1000 nm), they accumulate in tumors due to the enhanced permeation and accumulation (EPR) effect. They protect incorporated drugs during transport and help to solubilize drugs. The potential thermoresponsive behaviour of the polymers avoids the complicated techniques common to the preparation of micelles and other nanoparticles. The presence of hydrolytically labile groups in the structure of the polymers can be exploited to ensure the gradual degradation of the nanoparticles and excretion of the polymer from the organism. With the intention of preparing nanoparticles with thermoresponsive and pH-sensitive properties, amphiphilic diblock copolymers consisting of a fully hydrophilic block and an amphiphilic block will be prepared by RAFT polymerization. The associative behaviour of the copolymers in aqueous solutions, the formation and disintegration of nanoparticles or micelles will be studied by physicochemical methods, e.g. size-exclusion chromatography, dynamic light scattering, NMR and transmission electron microscopy. The proposed systems offer the possibility to transport in particular anticancer drugs.
Contact person: Ing. Michal Pechar, Ph.D., e-mail: pechar, tel.: 296 809 395
Place of work: Institute of Macromolecular Chemistry CAS, BIOCEV, Průmyslová 595, 252 50 Vestec
4) Actively targeted polymer cancerostatics
We will synthesize and characterize high-molecular-weight polymer carriers of therapeutics and diagnostics with enhanced accumulation in tumor tissue due to the so called enhanced permeability and retention (EPR) effect or due to the active targeting using recombinant protein ligands. We will prepare copolymers based on N-(2-hydroxypropyl)methacrylamide and other hydrophilic monomers including those containing in their structure bonds cleavable in human organism by various mechanisms. We will study various methods of covalent and non-covalent attachment of the targeting ligands to the polymer carriers; we will evaluate the structure-activity relationship of the synthesized polymer therapeutics and diagnostics. We will also investigate the effect of various cancerostatics on the antitumor activity of both targeted and non-targeted polymer conjugates.
Contact person: Ing. Michal Pechar, Ph.D., e-mail: pechar, tel.: 296 809 395
Place of work: Institute of Macromolecular Chemistry CAS, BIOCEV, Průmyslová 595, 252 50 Vestec