The research activities of the Department of biomedical polymers focus on the design and synthesis of highly hydrophilic and water-soluble polymers, the study of the interaction between synthetic and natural macromolecules, and the study of possible uses of the synthetic polymers, copolymers and their conjugates with natural macromolecules as actively- or passively-targeted carriers of drugs enabling controlled release of the drugs and other biologically active molecules at the place of the required therapeutic effect. The results of the basic research are exploited for the development of polymer nanomedicines and diagnostics, namely in the field of anti-cancer drugs.The Department is cooperating with leading biologically-oriented groups and companies in the Czech Republic and abroad.
The research activities of the Department focus on the following projects:
Polymers and polymer systems for targeted drug delivery (polymer therapeutics)
This project encompasses the study of the relationship between the structure, physico-chemical and biological properties of water-soluble polymers or supramolecular structure-forming polymer drug carriers and carriers of other biologically-active molecules designed as polymer therapeutics suitable for utilization in human medicine. Special attention is paid to the development of polymer anti-tumour drugs delivering polymer-bound cytotoxic drugs into solid tumours or to the receptors expressed in a membrane of the tumour cells and enabling cellular internalization and intracellular controlled release and activation of the delivered drugs. Synthesis of the polymer drugs is based on conjugation of reactive copolymers – polymer precursors – with targeting moieties and other biologically-active molecules (drugs). The structures of the polymer carriers are based on water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers forming polymer chains of various architecture or amphiphilic copolymers forming supramolecular and micellar structures in an aqueous environment.
At present the following systems are under study:
- high-molecular-weight biodegradable water-soluble polymer drug delivery systems with linear, branched, grafted or dendritic carrier structures enabling targeted delivery of cytotoxic drugs into rapidly proliferating tissues, namely solid tumours and their angiogenic vasculature (systems with passive targeting) and elimination of the carrier system after fulfilling its task;
- amphiphilic polymer systems forming micellar nanostructures in aqueous solutions suitable for development of passively- or actively-targeted carriers designed for delivery and controlled release of anti-cancer drugs;
- actively-targeted water-soluble polymer drug delivery systems containing the drug and targeting moiety (monoclonal or polyclonal antibody, its fragments (scFv, Fab), receptor-specific oligopeptide, hormone, etc.) enabling specific targeting of the drugs to the membrane receptors of tumour cells, cell membrane trafficking and intracellular release of the active molecule via enzymatically-catalyzed or pH-dependent chemical hydrolysis;
- biodegradable polymer nanomedicines based on linear multiblock water-soluble polymers composed of blocks of poly(ethylene glycol) interconnected with biodegradable (reductively, hydrolytically, enzymatically) oligopeptide or disulfide-group-containing sequences forming high-molecular-weight polymer-drug conjugates;
- conjugates of highly hydrophilic polymers with enzymes, hormones, antibodies or other biologically-active proteins/glycoproteins for vaccination and therapy;
- thermoresponsive polymers as carriers of drugs and/or radionuclides enabling local therapy and/or diagnosis of cancer diseases exploiting lower critical solution temperature (LCST) of the polymer carrier preset on a temperature close to body temperature. In these systems, the thermosensitivity of the system facilitates local therapy and long-term drug release.
Hybrid macromolecular stimuli-resposive systems
The aim of this project is the investigation of the associative behaviour of hydrophilic copolymers containing tailor-made multiple peptide blocks consisting of repeating pentapeptide or heptapeptide sequences, self-assembling into elastin-like structures or coiled coils in response to external stimuli (changes in pH, temperature). Except for its contribution to the general knowledge of the influence of external stimuli to secondary and tertiary peptide and protein structure, in this project we are using these properties for the design and preparation of a new class of “smart” stimuli-sensitive drug delivery systems and versatile double-barrelled systems enabling efficient targeting of drugs and gene delivery systems using antibody scFv fragments.
Polymers and polymer systems for combined therapy and diagnosis
This project deals with water-soluble polymers and polymer micellar systems as carriers enabling combined therapy and diagnosis. This type of polymer therapeutics is combining the activities of various ligands attached to the same carrier system. Polymer therapeutics combining the activity of two or more drugs differing in mechanism of action, activity of drug and radionuclide as radiotherapeutic or diagnostic or combining chemotherapy with hyperthermia, immunotherapy, radiotherapy or other clinical techniques are under study.
Polymer-based antibody mimetics - iBodies
We study in detail novel synthetic macromolecular systems (iBodies) based on water soluble N-(2-hydroxypropyl)methacrylamide copolymers designed to fully substitute antibodies in common biochemical methods. These synthetic copolymers with covalently attached low-molecular-weight functional groups, a targeting ligand, an affinity anchor and an imaging probe, imitating antibodies, were successfully tested in ELISA, flow cytometry, confocal microscopy, Western Blot, protein immobilization and immunoprecipitation methods. iBodies can be custom designed towards any protein of interest (provided a ligand is known) and tailored based on the intended applications. In cooperation with Institute of Organic Chemistry and Biochemistry and Charles University are now ready for routine lab use iBodies for purification of His-tag recombinant proteins. More information is available on www.ibodies.eu.