A5033182169- Nanoparticle-Based Drug Delivery
- Advanced Polymer Synthesis and Characterization
- Nanoplatforms for cancer theranostics
- RNA Interference and Gene Delivery
- Dendrimers and Hyperbranched Polymers
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Advanced Biosensing Techniques and Applications
- Graphene and Nanomaterials Applications
- Peptidase Inhibition and Analysis
- Polymer Surface Interaction Studies
- Radiopharmaceutical Chemistry and Applications
- Inflammasome and immune disorders
- Microfluidic and Capillary Electrophoresis Applications
- Click Chemistry and Applications
- Gout, Hyperuricemia, Uric Acid
- Single-cell and spatial transcriptomics
- Enzyme function and inhibition
- Crystallization and Solubility Studies
- Metal-Organic Frameworks: Synthesis and Applications
- DNA and Nucleic Acid Chemistry
- Lanthanide and Transition Metal Complexes
- Chemical Synthesis and Analysis
- Drug Solubulity and Delivery Systems
Czech Academy of Sciences, Institute of Macromolecular Chemistry
2015-2024
Czech Academy of Sciences
2018-2019
Charles University
2019
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2019
Institut d'Investigació Biomédica de Bellvitge
2013
University of Oxford
2013
Max Planck Institute of Colloids and Interfaces
2008
The nucleotide-binding-domain (NBD)-and leucine-rich repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant, and neurodegenerative diseases. Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated syndrome (CAPS). There is significant interest the discovery development diarylsulfonylurea Cytokine...
BackgroundOncolytic viruses are among the most powerful and selective cancer therapeutics under development showing robust activity in clinical trials, particularly when administered directly into tumor nodules. However, their intravenous administration to treat metastatic disease has been stymied by unfavorable pharmacokinetics inefficient accumulation penetration through tumors.
Abstract Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design development by bottom‐up approaches challenging, especially considering the non‐standardized process parameters in injection step. This work aims present a systematic step‐by‐step approach through Quality‐by‐Design (QbD) Design of Experiments (DoE)...
High‐molecular‐weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico‐chemical preliminary in vitro biological properties determined. The water‐soluble carriers prepared by grafting poly(amido amine) (PAMAM) dendrimers hetero‐telechelic N ‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. well‐defined...
Abstract Various biodegradable micellar polymer drug carriers based on N ‐(2‐hydroxypropyl)methacrylamide copolymers and their conjugates with doxorubicin are synthesized. The designed to treat solid tumors subsequently allow carrier elimination from the body. All self‐assemble in aqueous solution into supramolecular structures highly hydrophobic cholesterol derivatives core located hydrophilic shell. is released quickly micelles incubated at pH = 5.0 (modelling endosomes of tumor cells)....
N-(2-Hydroxypropyl)methacrylamide polymer precursors (pHPMA) with very narrow distribution of molecular weights and chain terminating in a single reactive group have big potential the synthesis various drug gene delivery systems. This paper shows that pHPMA can be prepared by reversible addition-fragmentation transfer (RAFT) polymerization; pHPMAs RAFT polymerization conducted to high conversions contained at α-end functional originated from both, agent (CTA) initiator (INI) ratio depending...
Abstract Short polypeptides with four pentad repeats, (VPGVG) 4 and (VPAVG) , were synthesised by manual fluorenylmethoxycarbonyl/ tert ‐butyl (Fmoc/ t ‐Bu) solid phase peptide synthesis using a convergent approach. In the next step, peptides coupled via their N ‐terminus activated semi‐telechelic poly(ethylene glycol) O ‐( ‐Fmoc‐2‐aminoethyl)‐ ′‐(2‐carboxyethyl)undeca(ethylene (Fmoc–PEG–COOH) to yield monodisperse Fmoc‐PEG‐peptide diblock copolymer. Both presence of terminal hydrophobic...
The synthesis, characterization and results of evaluation the biological behavior HPMA copolymer conjugates bearing anti‐cancer drugs doxorubicin mitomycin C are described. Two carrier types were synthesized: linear biodegradable high‐molecular‐weight diblock containing a degradable disulfide bond. polymer‐drug incubated in buffers modeling intracellular environment released more rapidly than those bloodstream conditions. Significant vitro vivo antitumor synergistic activity treatment EL‐4...
Glutamate carboxypeptidase II (GCPII) is a membrane protease overexpressed by prostate cancer cells and detected in the neovasculature of most solid tumors. Targeting GCPII with inhibitor-bearing nanoparticles can enable recognition, imaging, delivery treatments to cells. Compared methods based on antibodies other large biomolecules, inhibitor-mediated targeting benefits from low molecular weight inhibitor molecules, which are typically stable, easy-to-handle, able bind enzyme very high...
We developed a new simplified method for the synthesis of well-defined linear, diblock, or starlike N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer drug carriers using controlled reversible addition-fragmentation chain transfer polymerization. The prepared monodispersed polymers are after attachment intended enhanced anticancer therapy. This approach significantly reduces number required synthetic steps and minimizes consumption organic solvents during synthesis. As result, highly...
In vitro diagnostic methods face non-specific interactions increasing their background level and influencing the efficacy reproducibility. Currently, most important employed blocker of is bovine serum albumin (BSA), an animal product with some disadvantages like its batch-to-batch variability contamination RNases. Herein, we developed amphiphilic water-soluble synthetic copolymers based on highly biocompatible, non-immunogenic nontoxic N-2-(hydroxypropyl)methacrylamide (HPMA)-based or...
Proteases are directly involved in cancer pathogenesis. Expression of fibroblast activation protein (FAP) is upregulated stromal fibroblasts more than 90% epithelial cancers and associated with tumor progression. FAP expression minimal or absent most normal adult tissues, suggesting its promise as a target for the diagnosis treatment various cancers. Here, we report preparation polymer conjugate (an iBody) containing FAP-specific inhibitor targeting ligand. The iBody inhibits both human...
Vesicles bearing either cationic (amino) groups or zwitterionic (amino acid) on the surface were coated with a reactive multivalent hydrophilic N-(2-hydroxypropyl)methacrylamide polymer (PHPMA) and its positively charged analogue (3 mol % quaternary ammonium groups), both having thiazolidine-2-thione (TT) randomly distributed along chain. The vesicles dispersed in water at concentration of 1 mg/mL. effect charges model coating efficiency was evaluated. changes weight-average molecular...
In this study, we describe the design, synthesis, and physicochemical preliminary biological characteristics of new biodegradable, high-molecular-weight (HMW) drug delivery systems with star-like architectures bearing cytotoxic doxorubicin (DOX) attached by a hydrazone bond-containing spacer. The star polymers were synthesized grafting semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers on 2,2-bis(hydroxymethyl)propionic acid- (bis-MPA-) based polyester dendritic core....
Aqueous Cu-RDRP of<italic>N</italic>-(2-hydroxypropyl) methacrylamide was optimized to achieve co(polymers) of low dispersity and controlled molecular weight at high conversions.
Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze hydration of carbon dioxide to bicarbonate. They play a crucial role in number important physiological processes. CAIX is tumor-associated transmembrane isoenzyme overexpressed on the cell surface hypoxic solid tumors and represents validated target for cancer therapy diagnosis. Here, we describe development an N-(2-hydroxypropyl)methacrylamide-based copolymer conjugate (iBody) containing inhibitor selective targeting this...
Multidrug resistance (MDR) is often caused by the overexpression of efflux pumps, such as ABC transporters, in particular, P-glycoprotein (P-gp). Here, we investigate di- and tri- block amphiphilic polymer systems based on polypropylene glycol (PPO) copolymers (N-(2-hydroxypropyl)methacrylamide) (PHPMA) potential macromolecular inhibitors P-gp, concurrently, carriers drugs, passively targeting solid tumors enhanced permeability retention (EPR) effect. Interestingly, there were significant...