Polymer Nanotherapeutics for the Treatment of Cancer and Infectious Diseases

Polymer Nanotherapeutics for the Treatment of Cancer and Infectious Diseases

RNDr. Tomáš Etrych, Ph.D.

RNDr. Tomáš Etrych, Ph.D. — Project head

About us

The project focuses on the study of new types of polymer conjugates of biologically active compounds intended for the treatment of various types of oncological, infectious and inflammatory diseases with potential use in human medicine.

The structure of the proposed conjugates is based on biocompatible hydrophilic or amphiphilic polymeric carriers differing in composition, functional group valences, or polymer chain architecture to which various biologically active species – cancerostatic, peptide or protein antigens, antibodies, nucleic acids, inhibitors, etc. – are bound via stable or biodegradable linkages.

The application portfolio of the developed materials can be further expanded by incorporating fluorescent, radioisotopic or contrast agents into their structures, which can be used in the diagnosis of tumor diseases or in the image-guided surgery. Modern synthetic, polymerization and bioconjugation processes leading to the preparation of highly defined tailored materials as well as sophisticated physico-chemical and analytical techniques enabling their precise characterization will be used in this project.

Aims of the project

  • Development of new types of water-soluble and self-assembling supramolecular polymer carriers of drugs and contrast agents for the therapy and diagnostics of oncological and inflammatory diseases
  • Development of advanced antigen-based vaccines consisting of a nanoparticle-forming polymeric carrier, a peptide antigen and a synthetic adjuvant for the prophylaxis of infectious diseases and the personalized therapy of cancers
  • Development of high-molecular-weight polymer carriers of cancerostatics and immuno-therapeutics for combined chemo / immune therapy of oncological diseases
  • Development of new types of synthetic polycations and reactive hydrophilic polymers enabling the complexation or covalent binding of nucleic acids applicable in the treatment of oncological and hereditary diseases

Publications

2018

W. Islam, J. Fang, T.Etrych, P. Chytil, K. Ulbrich, A.Sakoguchi,K. Kusakabeb, H. Maeda, HPMA copolymer conjugate with pirarubicin: In vitro and ex vivo stability and drug release study, International Journal of Pharmaceutics 536 (2018) 108-118

M. Studenovsky, L. Sivak, O. Sedlacek, R. Konefal, V. Horkova, T. Etrych, M. Kovar, B. Rihova, M. Sirova, Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue, Journal of Controlled Release 269 (2018) 214–224.

2017

H. Kostková, L. Schindler, L. Kotrchová, M. Šírová, L. Kostka, T. Etrych, Star polymer-drug conjugates with pH-controlled drug release and carrier disintegration, Journal of Nanomaterials, Volume 2017, Article ID 8675435, 10 pages, (2017)

O. Slaby, R. Laga, O. Sedlacek, Therapeutic targeting of non-coding RNAs in cancer, Biochemical Journal 474 (2017) 4219–4251.

T. Etrych , K. Tsukigawa , H. Nakamura , P. Chytil , J. Fang, K. Ulbrich , M. Otagiri , H. Maeda, Comparison of the pharmacological and biological properties of HPMA copolymer-pirarubicin conjugates: A single-chain copolymer conjugate and its biodegradable tandem-diblock copolymer conjugate, European Journal of Pharmaceutical Sciences 106,(2017), 10-19

M. Šírová, J. Strohalm, P. Chytil, O. Lidický, B. Říhová, T. Etrych, The structure of polymer carrier controls efficacy of combination treatment of experimental tumors with HPMA copolymer conjugates carrying doxorubicin and docetaxel, Journal of Controlled Release 246, (2017) 1-11.

L. Sivak, V. Šubr, J. Tomala, B. Řihová, J.Strohalm, T. Etrych, M. Kovar, Overcoming multidrug resistance via simultaneous delivery of cytostatic drug and P-glycoprotein inhibitor to cancer cells by HPMA copolymer conjugate, Biomaterials 115 (2017) 65–80.

Braunová, L. Kostka, L. Sivák, L. Cuchalová, Z. Hvězdová, R. Laga, S. Filippov, P. Černoch, M. Pechar, O. Janoušková, M. Šírová, T. Etrych, Tumor-targeted micelle-forming block copolymers for overcoming of multidrug resistence, Journal of Controlled Release 245 (2017) 41–51.

2016

L. Beckert, L.Kostka, E. Kessel, A. Krhac Levacic, H. Kostkova, T. Etrych, U. Lächelt, E. Wagner, Acid-labile pHPMA modification of four-arm oligoaminoamide pDNA polyplexes balances shielding and gene transfer activity in vitro and in vivo, European Journal of Pharmaceutics and Biopharmaceutics 105 (2016) 85-96.

J. R. Francica, G. M. Lynn, R. Laga, M. G. Joyce, T. J. Ruckwardt, K. M. Moribito, M. Chen, R. Chaudhuri, B. Zhang, M. Sastry, K. Ko, M. Choe, M. Pechar, I. S. Georgiev, L. A. Kueltzo, L. W. Seymour, J. R. Mascola, P. D. Kwong, B. S. Graham, R. A. Seder, Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant, Bioconjugate chemistry 27 (2016) 2372-2385.

E. A. Lomkova, P. Chytil, O. Janoušková, T. Mueller, H. Lucas, S. K. Filippov, O. Trhlíková, P. A. Aleshunin, Y. A. Skorik, K. Ulbrich, T. Etrych, Biodegradable micellar HPMA-based polymer-drug conjugates with betulinic acid for passive tumor targeting, Biomacromolecules 17 (2016) 3493 – 3507.

G. Mužíková, R. Pola, R. Laga, M. Pechar, Biodegradable multiblock polymers based on N-(2-hydroxypropyl) methacrylamide designed as drug carriers for tumor-targeted delivery, Macromolecular Chemistry and Physics 217 (2016) 1690–1703.

G. Mužíková, R. Laga, Macromolecular systems for vaccine delivery, Physiological Research 65, (Suppl. 2): 203-216, (2016).

O. Lidický, M. Šírová, T. Etrych, HPMA copolymer-based polymer conjugates for the delivery and controlled release of retinoids, Physiological Research 65, (Suppl. 2): 233-241, (2016).

2015

Etrych T, Strohalm J, Sirova M, Tomalova B, Rossmann P, Rihova B, Ulbrich K, and Kovar M. High-molecular weight star conjugates containing docetaxel with high anti-tumor activity and low systemic toxicity in vivo. Polym. Chem. 2015, 6, 160-170.

2013

Sirova M, Kabesova M, Kovar L, Etrych T, Strohalm J, Ulbrich K, Rihova B. HPMA copolymer-bound doxorubicin induces immunogenic tumor cell death. Curr Med Chem. 2013;20(38):4815-26.

Team

RNDr. Tomáš Etrych, Ph.D.

RNDr.
Tomáš Etrych, Ph.D.

Member of the Board, Head of Group Development of Polymer Therapeutics and Diagnostics for Treatment and Diagnostic of Cancer Diseases

etrych@imc.cas.cz
+420325873804, +420325873806
Ing. Richard Laga, Ph.D.

Ing.
Richard Laga, Ph.D.

laga@imc.cas.cz
+420325873803, +420325873804
Ing. Gabriela Mužíková

Ing.
Gabriela Mužíková

PhD. student

muzikova@imc.cas.cz
+420325873803
Mgr. Ondřej Lidický

Mgr.
Ondřej Lidický

PhD. student

lidicky@imc.cas.cz
+420325873803
Ing. Lenka Kotrchová

Ing.
Lenka Kotrchová

PhD. student

kotrchova@imc.cas.cz
Ing. Ladislav Androvič

Ing.
Ladislav Androvič

androvic@imc.cas.cz
+420325873803