Martin Konhefr - Scientist and aviator
I am part of the implementation group at the Institute of Chemical Processes at the Czech Academy of Sciences, which cooperates with several other institutes of the Czech Academy of Sciences and research groups at several universities on a project focusing on regenerative medicine.
“Regenerative medicine is a new prospective field focused on repairing or replacing tissues or organs that have lost their function due to old age, disease, damage or congenital defects. It is a multidisciplinary field including tissue engineering, molecular biology and nanotechnology. The research agenda of the project includes the creation and development of an excellent research Center focused on R&D in the field of regenerative medicine therapeutic methods, which have the potential in the longer term to create applicable results of research and development, and which will contribute to the development of the competitiveness of the Czech Republic in the given field. The excellence and uniqueness of the project lies in the fact that its research intentions aim at restoring tissues whose damage is not yet curable, or their regenerative capacity is greatly limited. These include mainly damage to the nerve tissue of the brain and spinal cord, including the problem of neurodegeneration and retinal degeneration, as well as the replacement of small-diameter blood vessels, which are still missing on the market (or in clinical practice), and last but not least the active healing of chronic wounds and osteochondral defects, which also belong to the serious problems of modern civilized society. The unifying element of the whole project are the “Medical devices for modern therapies", namely products for gene therapy, somatic cell therapy and tissue engineering products." - that's the annotation to this project from our cooperating BUT
As part of this project in the laboratory of Bioorganic Chemistry and Biomaterials, we prepare and characterise a completely novel platform of multivariable dendrimers (branched polymer molecules) based on easily functionalizable carbosilanes, which will be used as carriers for planned regenerative applications in the next phases of the project. In our case, it is primarily an application in the treatment of osteochondral defects. Our carriers should transport (not only) growth factors more easily and efficiently to target sites of these defects supporting there the repair of damaged or missing tissue.
Development of treatment of osteochondral defects
Projekt: Excellence Research in Regenerative Medicine (ExRegMed, OP JAK)
Principal Investigator at ICPF CAS: Ing. Tomáš Strašák, Ph.D.
Duration of the project: 10/2023–06/2028
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This is my main project to which I devoted most of my scientific effort. As introduced in the My work tab, the ROS-responsive smart materials were natural continuation of the studies from my PhD topic – the boronic acids and electrochemistry of (amino)ferrocenes merged together.
Reactive oxygen species (ROS) have been associated with cancer for long time. Both boronic acid and ferrocene are involved in the design and development of ROS‑related therapeutic agents. In this context, ROS-activated prodrugs are very promising because ROS represent the activating stimuli causing release of the appended active agent from the structure of the prodrug via interactions with boronic acid moieties. Iron atom in ferrocenes (especially in aminoferrocene) serves as a ROS inducer in cells, thus, it can produce enough ROS to kill the cell via ferroptosis (special kind of Fe-dependent apoptosis).
We did general research mainly in the synthetic material chemistry (NMR, EPR, MS, Raman, FTIR, UV-vis) and electrochemistry of new candidates for the ROS-responsive prodrugs to reveal new concepts of advanced drug delivery and release with low side effect toxicity as-designed. Some cytotoxicity of the ferrocenyliminoboronates as first model of ROS-related agents have been already tested with the result of their comparable cytotoxicity to other aminoferrocenyl prodrugs. Next effort should be devoted to reconsider responsive structures, preparation of new candidates acting via concepts of ROS-responsivity and further biochemical testing of their properties in cells.
If you like the concept of the ROS-responsiveness, have got a similar expertise in supramolecular, pharmacological or medical field and would like to collaborate, please, contact me or Dr. Lacina. We would like to find a partner with a background in microbiology for testing of some of our compounds with Mycobacterium tuberculosis.
ROS-induced drug release based on interactions of ferrocenylboronates
Code of project: 19-16273Y
PI at MUNI: Mgr. Karel Lacina, Ph.D.
Project period: 01/2019–12/2021
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As part of a long-term collaboration with Prof. Trnková, I was involved in a small project dedicated to the interaction of cuprous ion with nitrogen-containing nucleobases. These can be both the purine bases or their aminopurine and methylated analogues. Copper is one of the essential elements important for the proper functioning of an organism, especially metabolic, transport and synthetic processes. The binding of the nucleobase and the copper atom in its possible oxidation states and associated redox behaviour (Cu2+/Cu+) has a significant effect on the structure, conformation and stability of such complexes and, as a result, biological structures such as enzymes.
Initially, Cu(I) interactions with aminopurines were only observed in situ on electrode surfaces when measuring copper electrochemistry in aminopurine solutions. Recently, despite the general instability of the Cu+ cation, we have been able to prepare a stable material containing a Cu(I)Adenine complex for further study of its structure, stability and stereochemistry and understanding these interactions in the first phase using synthetic material chemistry (63Cu NMR, EPR, Raman, FTIR, MS). The next phase should include further biophysical structural (RTG) and electrochemical studies of these interactions.
For more information and possible involvement in the project, just contact me.
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In 2019, I spent a quarter of the year at Josai University in Japan as a visiting student from MUNI (thanks to the Erasmus+ ICM, see Travelling category in My Blog). Our research group at MUNI thus established a new cooperation with the research group of Prof. Egawa.
For all three months of my stay there, I predominantly worked on novel approaches for the intended purpose of molecular recognition, saccharide sensing and, in connection with that, also controlled drug delivery system which involved ferrocenes and boronic acids. New concept of injectable sol-gel with worm-like micelles (WLMs) has been further developed using electrochemical ferrocene labels. WLMs or rod-like micelles grow in one direction as a rod. From specific concentration, they form a 3D network of entangled micelles, predominantly via intermolecular interactions. Depending on states of micelles, their solutions show different physical properties, i.e. sol or gel appearance.
This exciting topic is closely related to my general interest in responsive smart materials. The saccharide or diol-responsive smart materials are highly desired due to their possible utilization in biomedical research, e.g. for controlling of blood sugar. The collaborative research of Prof. Egawa is focused on the controlling of diol-responsiveness innate for the smart material as-designed. Such smart materials will have intrinsic feedback of their surroundings which may lead to a release of their cargo (e.g. carried insulin). Herein, we would like to explore and widen possible options for studying such responsive systems, e.g. by utilizing the electrochemistry for description of the processes associated with various levels of diols in the system (similarly as various levels of glucose in blood).
If you are interesting in the concept of diol-responsiveness, please, contact me for more information. At least but not last, a similar project involving insulin in the frame of saccharide sensing and control issues can be seen in the Sensor for detection of diabetes tab.
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