Research activities of the Department consist mainly of the design, synthesis, and physico-chemical and biological evaluation of stimuli-responsive water-soluble or micelle-forming polymer materials intended for medical use as carriers of drugs, diagnostics, genes, or other biologically active molecules. These polymer nanomedicines improve the pharmacokinetics of the carried molecules, remove their side-effects and enable the localized treatment specifically in the target tissue, i.e. cancerous tissue, inflamed tissue or tissue after bacterial infection. Our research aim is the development of highly effective polymer nanomedicines for anti-cancer, anti-inflammatory, or antibiotic treatment, in order to improve the patient´s quality of life.
Polymers for Imaging and Diagnostics
Despite notable advances in the healthcare provided to clinical patients, early and accurate tumor diagnosis together with efficient and safe cancer therapy belong to the most serious medical challenges of the 21st century. Advanced imaging of tumor tissue using satisfactory diagnostic methods is the key point for successful treatment of human malignancies. As part of our research, we develop polymer diagnostics that enable the precise detection of solid tumors, e.g. probes for the fluorescence-guided surgery for head and neck, and breast tumors with a high contrast of normal/tumor tissue.
Theranostics is an emerging field of medicine in which drugs and/or techniques are uniquely combined to simultaneously or sequentially diagnose and treat medical issues. The ability to acquire a diagnosis and administer therapy in one package is a challenge for contemporary medicine. This approach potentially allows one to bypass some of the undesirable biological effects that may arise when these strategies are employed separately. Thus, the inseparable part of the Department’s research is based on the combination of polymer-bound therapeutics and diagnostics, into the so-called polymer theranostics. They can facilitate the visualization of treated target tissue, and thus, enable the observation of the therapy progress. Various nanomedicines containing both anticancer drug and far-red or near-infrared fluorescent dyes for fluorescent imaging techniques, or radionuclide ligands for positron emission tomography (PET) have been studied and evaluated in vivo for their theranostic properties. Moreover, the use of polymer theranostics can eliminate the unnecessary treatment of patients for whom such therapy is not appropriate, resulting in significant drug cost savings for the healthcare system.
Amphiphilic polymers forming micellar nanostructures
Our attention focuses also on various methacrylamide-based amphiphilic copolymers, i.e. polymers consisting of hydrophilic and hydrophobic parts, forming micellar nanostructures and on their utilization as carriers of anti-cancer drugs.
Amphiphilic copolymers self-assembling into micelles or nanoaggregates provide many advantages. Due to their increased size in aqueous solutions, they can serve as a long-circulating drug carrier significantly improving drug accumulation in solid tumors due to the enhanced permeability and retention (EPR) effect. In addition, a long-circulating polymer depo of low-molecular-weight drugs can also be used in the advanced treatment of hematological malignancies, where the EPR effect cannot be applied or is suppressed. Owing to the covalent and concurrently non-covalent incorporation of active compounds to the polymer carrier, a broad range of biologically active substances could be jointly delivered and thus potentiate the treatment.
Antibody mimetics “iBodies”
iBodies®, the novel macromolecules designed to fully substitute antibodies in common biochemical methods, are currently distributed for routine use in laboratories. iBodies® were successfully utilized in ELISA, flow cytometry, confocal microscopy, Western Blotting, protein immobilization, and immunoprecipitation methods. These fully synthetic antibody mimetics consist of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer backbone decorated with low-molecular-weight functional moieties: a targeting ligand, an affinity anchor, and an imaging probe. General schematic structure of representative iBody is shown below. iBodies® can be tailor-made for any protein of interest (provided a ligand is known) and adjusted to the intended applications. More information can be found on the ibodies.eu. Currently, selected iBodies are distributed for routine use in laboratories through Ximbio company.
Polymer nanomedicines overcoming biological barriers
In contemporary oncological therapy, overcoming of the biological barriers, i.e. multidrug resistance (MDR) or defective tumor vasculature and blood flow, is one of the key factors restricting the therapy outcome in most cancer treatment schedules. By employing new polymer structures and various adjuvant agents we develop new polymer nanomedicines, which can overcome MDR, or augment the EPR effect by various enhancers, thus enhancing the therapy outcome of poorly manageable malignancies. Indeed, we aim to develop effective-by-design polymer system, which will overcome the biological barriers due to its inner structure.
Nanomedicines for personalized therapy
Personalized medicine is a medical model that tailors all medical interventions and pharmacotherapy to each individual patient based on their predicted response or risk of disease. Nanotechnology-based approaches have demonstrated amazing potential to transform general ‘one drug to fit all’ medicine to highly personalized treatment modalities. In our research, the nanosized carriers are engineered via bottom-up strategy to a highly customizable extent, hence enabling very needed cost-effective personalized approaches by integrating detailed information about the desired tissue of each patient into the design of nanomedicines, thus allowing highly effective and precise therapy with low risk of side effects.
Polymers for Targeted therapy and drug-free nanotherapeutics
Polymer nanomedicines with affinity for various ligands, namely oligopeptides, monoclonal antibodies, or recombinant antibody fragments, can be employed for targeting at the desired malignant tissues and cells and thus improve the poorly treatable tumors, such as lymphomas. Another approach based on “drug-free nanotherapeutics” consists of the utilization of glycoconjugates, i.e. polymer carriers decorated by tailor-made oligosaccharides or glycomimetics with high affinity for lectin ligands, molecules located on specific tumor cells. Recently, our glycoconjugates proved excellent affinity for human lectins associated with the tumor growth and invasiveness, thus potentially diminishing the tumor progression in the body.
Advanced polymer carrier structures
The inner structure of polymer carriers plays a crucial role in the properties and biological effectiveness of the nanomedicines. We aim to develop novel synthetic strategies for the synthesis of well-defined linear, diblock, graft or star-like polymer carriers using controlled polymerization techniques and advanced methods of contemporary organic chemistry. The high-molecular-weight biocompatible and biodegradable polymer carriers have been designed, synthesized, and evaluated thoroughly regarding their potential in controlled drug delivery to solid tumors or inflamed tissue.