Ta strona wykorzystuje ciasteczka ("cookies") w celu zapewnienia maksymalnej wygody w korzystaniu z naszego serwisu. Czy wyrażasz na to zgodę?

Czytaj więcej

Chemistry for medicine

Potential analgesic drugs

Prof. Aleksandra Misicka-Kęsik, PhD DSc; Ewa Witkowska, PhD; Beata Wileńska, PhD Eng

Prof. Barbara Przewłocka, PhD DSc (Maj Institute of Pharmacology Polish Academy of Sciences)

Neuropathic pain results from damage or disease of the nervous system. This particular type of pain often becomes chronic and the effectiveness of currently available therapies is limited: almost half of patients do not experience improvement with any of the available drugs. Therefore, developing a new pharmacotherapeutic strategy for the treatment of neuropathic pain is one of the fundamental medical challenges of modern times.

In search of new therapies for neuropathic pain, two collaborating teams: the Peptide Laboratory team from the Faculty of Chemistry, University of Warsaw, headed by prof. Aleksandra Misicka-Kęsik, and the team from the Maj Institute of Pharmacology of the Polish Academy of Sciences in Krakow, headed by Prof. Barbara Przewłocka developed peptidomimetics showing high analgesic activity in an animal model of neuropathic pain. The structure of these compounds for use in neuropathic pain has been claimed, and American and Japanese patents have already been granted.

The inventors founded the company, Neuro-OpioMel sp. z o.o., which received a grant from the National Center for Research and Development in 2021 for further research on the developed peptidomimetics as potential drugs in the treatment of neuropathic pain. In order to conduct these studies, the company purchased a license from the University of Warsaw and the Maj Institute of Pharmacology of the Polish Academy of Sciences. The results of preclinical studies conducted so far on animals give hope for the development of a new drug for the treatment of neuropathic pain.

Selected publications:

  1. Misicka-Kęsik, E. Witkowska, B. Wileńska, B. Przewłocka, J. Mika, J. Starnowska-Sokół, A. Piotrowska-Murzyn, “Novel hybrid peptidomimetics for use in neuropathic pain” 7395149 (Japonia), US11041010
  2. Starnowska-Sokół, A.Piotrowska, J.Bogacka, W. Makuch, J. Mika, E. Witkowska, M. Godlewska, J. Osiejuk, S. Gątarz, A. Misicka, B. Przewłocka, “Novel hybrid compounds, opioid agonist+melanocortin 4 receptor antagonist, as efficient analgesics in mouse chronic constriction injury model of neuropathic pain” Neuropharmacology, 2020, 178, 108232, DOI: https://doi.org/10.1016/j.neuropharm.2020.108232
  3. Piotrowska, J. Starnowska-Sokół, W. Makuch, J. Mika, E. Witkowska, D. Tymecka, A. Ignaczak, B. Wilenska, A. Misicka, B. Przewłocka, “Novel bifunctional hybrid compounds designed to enhance the effects of opioids and antagonize the pronociceptive effects of nonopioid peptides as potent analgesics in a rat model of neuropathic pain” PAIN, 2021, 162,  432, DOI: http://dx.doi.org/10.1097/j.pain.0000000000002045
  4. Witkowska, M. Godlewska, J. Osiejuk, S. Gątarz, B. Wileńska, K. Kosińska, J. Starnowska-Sokół, A. Piotrowska, P. F. J. Lipiński, J. Matalińska, J. Dyniewicz, P. K. Halik, E. Gniazdowska, B. Przewłocka, A. Misicka, “Bifunctional opioid/melanocortin peptidomimetics for use in neuropathic pain: variation in the type and length of the linker connecting the two pharmacophores” Int. J. Mol. Sci. 2022, 23, 674, DOI: https://doi.org/10.3390/ijms23020674
Potential drugs for Alzheimer disease

Anna Zawadzka, PhD; Maciej Mazur, PhD DSc, Assoc. Prof.; Maciej Chotkowski, PhD DSc, Assoc. Prof. and the team

Alzheimer’s disease has long posed a significant challenge for the medical community. Despite extensive research, its exact causes remain elusive, and current treatments primarily aim to slow its progression and alleviate symptoms like memory loss and cognitive decline. This devastating condition not only affects those diagnosed but also places a heavy burden on their loved ones. As such, any new advancement in Alzheimer’s treatment garners widespread attention.

The newly synthesized compound, a tetrahydroacridine derivative (CHDA) shows potential not only for the treatment but also for diagnostic purposes. CHDA has a strong affinity for gold, particularly gold nanoparticles, with which it forms stable conjugates. This interaction was confirmed through various spectroscopic and electrochemical methods. In vitro tests have shown that both the free compound and its gold-conjugated form inhibit activity of acetylcholinesterase, an enzyme associated with the progression of Alzheimer’s disease. Importantly, these studies also indicate that the compound is non-toxic.

Furthermore, when CHDA is conjugated with nanoradiogold particles (Au-198), it opens up new possibilities for medical imaging, potentially enhancing diagnostic techniques for Alzheimer’s and other neurodegenerative diseases. Specifically, the Au-198 radioisotope can be used in SPECT imaging. With this approach, the movement of the conjugate within the body could be tracked using SPECT, leading to a more effective therapeutic outcome. This breakthrough brings renewed hope in the ongoing battle against one of the most challenging medical conditions of our time.

Selected publications:

  1. Mojzych, A. Zawadzka, K. Kaczynska, P. Wojciechowski, D. Zając, M. Chotkowski, K. Wiktorska, J.K. Maurin, M. Mazur, “Tetrahydroacridine derivative and its conjugate with gold nanoparticles: Promising agents for the treatment of Alzheimer’s disease” Phys. Chem. Chem. Phys. 2023, 25, 16796, DOI: https://doi.org/10.1039/D3CP00767G
  2. Mojzych, A. Zawadzka, K. Andrzejewski, M. Jampolska, Z. Bednarikova, M. Gancar, Z. Gazova, M. Mazur, K. Kaczyńska, “A novel tetrahydroacridine derivative with potent acetylcholinesterase inhibitory properties and dissociative capability against Aβ42 fibrils confirmed by in vitro studies.” Int. J. Mol. Sci. 2024, 25, 10072, DOI: https://doi.org/10.3390/ijms251810072
Personal medicine

Prof. Anna Nowicka, PhD DSc; Prof. Sławomir Sęk, PhD DSc; Prof. Ireneusz P. Grudziński, PhD DSc (Faculty of Pharmacy) and teams

POLNOR 2019 „Theranostic Exosomes in Personalized Cancer Nanomedicine TEPCAN”

Exosomes (EVs) are extracellular vesicles secreted by most eukaryotic cells that play a key role in communication between diverse cells – they carry chemical and biological control signals. The use of patient-derived exosomes allows their use in personalized cancer therapy. As part of an international Polish-Norwegian collaboration, prof. Anna Nowicka’s team, together with the team of prof. Slawomir Sęk and prof. Ireneusz Grudziński from the WUM Faculty of Pharmacy, has proposed an effective way to improve the effectiveness of lung cancer treatment using magnetic hyperthermia, a promising therapeutic strategy that aims to destroy cancer cells by exposing them to an alternating magnetic field to heat a given area to a temperature in the range of 40-43 °C. This effect was achieved using exosomes taken from patients and loaded with newly synthesized magnetic iron(III) oxide nanoparticles doped with magnesium. In addition, to direct the delivery of the proposed system to tumor cells, the exosomes were functionalized with a self-navigating molecule a heptapeptide with the PTHTRWA amino acid sequence, which has high affinity for the integrin α5β1, one of the main components of the tumor cell membrane. Magnetic resonance imagining showed that the as-bioengineered PTHTRWA-exosomes loaded with superparamagnetic nanoparticles (MNPs) cargos reach the growing tumor when dosed intravenously in NUDE Balb/c mice bearing lung cancer. Preclinical safety assays did not evidence any cytotoxic and genotoxic effects of the PTHTRWA-bioengineered exosomes.

Selected publications:

  1. Kowalczyk, D. Dziubak, A. Kasprzak, K. Sobczak, M. Ruzycka-Ayoush, M. Bamburowicz-Klimkowska, S. Sęk, I. Rios-Mondragon, T. Żołek, E. Runden-Pran, S. Shaposhnikov, M. R. Cimpan, M. Dusinska, I. P. Grudzinski, A. M. Nowicka, “Surface-bioengineered extracellular vesicles seeking molecular biotargets in lung cancer cells” ACS Applied Materials & Interfaces, 2024, 6, 31997, DOI: https://pubs.acs.org/doi/10.1021/acsami.4c04265
  2. M. Nowicka, M. Ruzycka-Ayoush, A. Kasprzak, A. Kowalczyk, M. Bamburowicz-Klimkowska, M. Sikorska, K. Sobczak, M. Donten, A. Ruszczynska, J. Nowakowska, I. P. Grudzinski, „Application of biocompatible and ultrastable superparamagnetic iron(iii) oxide nanoparticles doped with magnesium for efficient magnetic fluid hyperthermia in lung cancer cells” Journal of Materials Chemistry B, 2023, 11, 4028, DOI: https://doi.org/10.1039/D3TB00167A