Jindrich Kopecek

Jindrich Kopecek, PhD, DSc

Languages spoken: Russian, German, English, Czech

Academic Information

Departments Primary - Molecular Pharmaceutics

Jindrich Kopecek, PhD, DSc, is a distinguished professor in the Departments of Pharmaceutics, Pharmaceutical Chemistry, and Bioengineering at the University of Utah. He is also a member of the Experimental Therapeutics Program at Huntsman Cancer Institute.

Kopecek's research interests include the design, synthesis, and characterization of biorecognizable biomedical polymers. He focuses on the development of targeted anticancer drugs, particularly to treat ovarian cancer.

Kopecek received a master's degree from the Institute of Chemical Technology, Czechoslovakia, a PhD from the Institute of Macromolecular Chemistry, Czechoslovakia, and a DSc from the Czechoslovak Academy of Sciences.

Research Statement

Research in the Kope'ek Biomedical Polymers Laboratory focuses on two main areas:

Macromolecular therapeutics. Recent research focuses on the design of backbone degradable, long-circulating polymer carriers that contain enzymatically degradable oligopeptide sequences in the main chain. These N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug (epirubicin, gemcitabine, paclitaxel) conjugates have demonstrated enhanced efficacy in the treatment of animal tumor models when compared to non-degradable HPMA copolymer conjugates or free drugs. Combination therapy targeting both tumor-initiating and differentiated cancer cell populations is also studied.

Drug-free macromolecular therapeutics. A new therapeutic approach for the treatment of B cell malignancies has been developed.The effectiveness of the new system is based on biorecognition events without the participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. Drug-free macromolecular therapeutics (DFMT) are composed from two nanoconjugates: 1) bispecific engager, Fab’-MOTIF1 (anti-CD20 Fab’ fragment conjugated with coiled-coil forming peptide or morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MOTIF2)X (HPMA copolymer or human serum albumin grafted with multiple copies of complementary oligopeptide or morpholino oligonucleotide).The efficacy of the system was validated in vitro, in vivo and on cells isolated from patients with various subtypes of B cell malignancies.

Education History

Graduate Training Institute of Chemical Technology
 MS
Doctoral Training Czechoslovak Academy of Sciences
 PhD
Postdoctoral Fellowship National Research Council of Canada
 Postdoctoral Fellow
Doctoral Training Czechoslovak Academy of Sciences
 DSc

Selected Publications

Journal Article

  1. Kope'ek J, Yang (2012). Smart self-assembled hybrid hydrogel biomaterials. Angewandte Chemie (International ed. in English), 51(30), 7396-417.
  2. Wu K, Liu J, Johnson RN, Yang J, Kopecek (2010). Drug-free macromolecular therapeutics: induction of apoptosis by coiled-coil-mediated cross-linking of antigens on the cell surface. Angewandte Chemie (International ed. in English), 49(8), 1451-5.
  3. Low SA, Yang J, Kope'ek (2014). Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics. Bioconjugate chemistry, 25(11), 2012-20.
  4. Johnson RN, Kopecková P, Kopecek (2009). Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20. Bioconjugate chemistry, 20(1), 129-37.
  5. Wang D, Miller SC, Shlyakhtenko LS, Portillo AM, Liu XM, Papangkorn K, Kopecková P, Lyubchenko Y, Higuchi WI, Kopecek (2007). Osteotropic Peptide that differentiates functional domains of the skeleton. Bioconjugate chemistry, 18(5), 1375-8.
  6. Yang J, Li L, Kope'ek (2019). Biorecognition: A key to drug-free macromolecular therapeutics. Biomaterials, 190-191, 11-23.
  7. Zhou Y, Yang J, Kope'ek (2012). Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells. Biomaterials, 33(6), 1863-72.
  8. Wu LC, Yang J, Kope'ek (2011). Hybrid hydrogels self-assembled from graft copolymers containing complementary ß-sheets as hydroxyapatite nucleation scaffolds. Biomaterials, 32(23), 5341-53.
  9. Kopecek (2007). Hydrogel biomaterials: a smart future?. Biomaterials, 28(34), 5185-92.
  10. Yuan W, Yang J, Kopecková P, Kopecek (2008). Smart hydrogels containing adenylate kinase: translating substrate recognition into macroscopic motion. Journal of the American Chemical Society, 130(47), 15760-1.
  11. Peng ZH, Kope'ek (2015). Enhancing Accumulation and Penetration of HPMA Copolymer-Doxorubicin Conjugates in 2D and 3D Prostate Cancer Cells via iRGD Conjugation with an MMP-2 Cleavable Spacer. Journal of the American Chemical Society, 137(21), 6726-9.
  12. Luo K, Yang J, Kope'ková P, Kope'ek (2011). Biodegradable Multiblock Poly[N-(2-hydroxypropyl)methacrylamide] via Reversible Addition-Fragmentation Chain Transfer Polymerization and Click Chemistry. Macromolecules, 44(8), 2481-2488.
  13. Du'ek K, Du'ková-Smr'ková M, Yang J, Kope'ek (2009). Coiled-Coil Hydrogels. Effect of Grafted Copolymer Composition and Cyclization on Gelation. Macromolecules, 42(6), 2265-2274.
  14. Pan H, Kopecková P, Liu J, Wang D, Miller SC, Kopecek (2007). Stability in plasmas of various species of HPMA copolymer-PGE1 conjugates. Pharmaceutical research, 24(12), 2270-80.
  15. Xu C, Kopecek (2008). Genetically engineered block copolymers: influence of the length and structure of the coiled-coil blocks on hydrogel self-assembly. Pharmaceutical research, 25(3), 674-82.
  16. Zhang R, Yang J, Sima M, Zhou Y, Kope'ek (2014). Sequential combination therapy of ovarian cancer with degradable N-(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates. Proceedings of the National Academy of Sciences of the United States of America, 111(33), 12181-6.
  17. Zhou Y, Kope'ek (2013). Biological rationale for the design of polymeric anti-cancer nanomedicines. Journal of drug targeting, 21(1), 1-26.
  18. Ding H, Kopecková P, Kopecek (2007). Self-association properties of HPMA copolymers containing an amphipathic heptapeptide. Journal of drug targeting, 15(7-8), 465-74.
  19. Li L, Yang J, Wang J, Kope'ek (2019). Drug-free macromolecular therapeutics exhibit amplified apoptosis in G2/M phase arrested cells. Journal of drug targeting, 27(5-6), 566-572.
  20. Zhou Y, Yang J, Zhang R, Kope'ek (2015). Combination therapy of prostate cancer with HPMA copolymer conjugates containing PI3K/mTOR inhibitor and docetaxel. European journal of pharmaceutics and biopharmaceutics, 89, 107-15.
  21. Duangjai A, Luo K, Zhou Y, Yang J, Kope'ek (2014). Combination cytotoxicity of backbone degradable HPMA copolymer gemcitabine and platinum conjugates toward human ovarian carcinoma cells. European journal of pharmaceutics and biopharmaceutics, 87(1), 187-96.
  22. Zhang L, Fang Y, Yang J, Kope'ek (2017). Drug-free macromolecular therapeutics: Impact of structure on induction of apoptosis in Raji B cells. Journal of controlled release, 263, 139-150.
  23. Yang J, Kope'ek (2016). Design of smart HPMA copolymer-based nanomedicines. Journal of controlled release, 240, 9-23.
  24. Li L, Yang J, Soodvilai S, Wang J, Opanasopit P, Kope'ek (2019). Drug-free albumin-triggered sensitization of cancer cells to anticancer drugs. Journal of controlled release, 293, 84-93.
  25. Hartley JM, Zhang R, Gudheti M, Yang J, Kope'ek (2016). Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM. Journal of controlled release, 231, 50-9.
  26. Chu TW, Feng J, Yang J, Kope'ek (2015). Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation. Journal of controlled release, 220(Pt B), 608-16.
  27. Yang J, Zhang R, Radford DC, Kope'ek (2015). FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy. Journal of controlled release, 218, 36-44.
  28. Zhou Y, Yang J, Rhim JS, Kope'ek (2013). HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects. Journal of controlled release, 172(3), 946-53.
  29. Zhang R, Luo K, Yang J, Sima M, Sun Y, Janát-Amsbury MM, Kope'ek (2013). Synthesis and evaluation of a backbone biodegradable multiblock HPMA copolymer nanocarrier for the systemic delivery of paclitaxel. Journal of controlled release, 166(1), 66-74.
  30. Liu J, Bauer H, Callahan J, Kopecková P, Pan H, Kopecek (2010). Endocytic uptake of a large array of HPMA copolymers: Elucidation into the dependence on the physicochemical characteristics. Journal of controlled release, 143(1), 71-9.
  31. Malugin A, Kopecková P, Kopecek (2007). Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells. Journal of controlled release, 124(1-2), 6-10.
  32. Zhang L, Zhang R, Yang J, Wang J, Kope'ek (2016). Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate. Journal of controlled release, 235, 306-318.
  33. Yang J, Zhang R, Christopher Radford D, Kope'ek (2015). Design and synthesis of FRET-trackable HPMA-based biodegradable conjugates for drug/gene delivery. Journal of controlled release, 213, e58.
  34. Zhang L, Fang Y, Kope'ek J, Yang (2017). A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin's lymphomas. European journal of pharmaceutical sciences, 103, 36-46.
  35. Hongrapipat J, Kopecková P, Prakongpan S, Kopecek (2008). Enhanced antitumor activity of combinations of free and HPMA copolymer-bound drugs. International journal of pharmaceutics, 351(1-2), 259-70.
  36. Larson N, Yang J, Ray A, Cheney DL, Ghandehari H, Kope'ek (2013). Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment. International journal of pharmaceutics, 454(1), 435-43.
  37. Kope'ek (2013). Polymer-drug conjugates: origins, progress to date and future directions. Advanced drug delivery reviews, 65(1), 49-59.
  38. Low SA, Kope'ek (2012). Targeting polymer therapeutics to bone. Advanced drug delivery reviews, 64(12), 1189-204.
  39. Shiah JG, Konák C, Spikes JD, Kopecek (1998). Influence of pH on aggregation and photoproperties of n-(2-hydroxypropyl)methacrylamide copolymer-meso-chlorin e6 conjugates. Drug delivery, 5(2), 119-26.
  40. Johnson RN, Kope'ková P, Kope'ek (2012). Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates. Biomacromolecules, 13(3), 727-35.
  41. Pan H, Yang J, Kopecková P, Kopecek (2011). Backbone degradable multiblock N-(2-hydroxypropyl)methacrylamide copolymer conjugates via reversible addition-fragmentation chain transfer polymerization and thiol-ene coupling reaction. Biomacromolecules, 12(1), 247-52.
  42. Callahan J, Kope'kov P, Kope'ek (2009). Intracellular trafficking and subcellular distribution of a large array of HPMA copolymers. Biomacromolecules, 10(7), 1704-14.
  43. Yang J, Wu K, Konák C, Kopecek (2008). Dynamic light scattering study of self-assembly of HPMA hybrid graft copolymers. Biomacromolecules, 9(2), 510-7.
  44. Sheparovych R, Roiter Y, Yang J, Kope'ek J, Minko (2009). Stimuli-responsive properties of peptide-based copolymers studied via directional growth of self-assembled patterns on solid substrate. Biomacromolecules, 10(7), 1955-61.
  45. Hartley JM, Chu TW, Peterson EM, Zhang R, Yang J, Harris J, Kope'ek (2015). Super-Resolution Imaging and Quantitative Analysis of Membrane Protein/Lipid Raft Clustering Mediated by Cell-Surface Self-Assembly of Hybrid Nanoconjugates. Chembiochem, 16(12), 1725-9.
  46. Kopecek (2010). Biomaterials and drug delivery: past, present, and future. Molecular pharmaceutics, 7(4), 922-5.
  47. Hongrapipat J, Kopecková P, Liu J, Prakongpan S, Kopecek (2008). Combination chemotherapy and photodynamic therapy with fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells. Molecular pharmaceutics, 5(5), 696-709.
  48. Pan H, Sima M, Kopecková P, Wu K, Gao S, Liu J, Wang D, Miller SC, Kopecek (2008). Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates. Molecular pharmaceutics, 5(4), 548-58.
  49. Zhang L, Fang Y, Li L, Yang J, Radford DC, Kope'ek (2018). Human Serum Albumin-Based Drug-Free Macromolecular Therapeutics: Apoptosis Induction by Coiled-Coil-Mediated Cross-Linking of CD20 Antigens on Lymphoma B Cell Surface. Macromolecular bioscience, 18(11), e1800224.
  50. Li L, Yang J, Wang J, Kope'ek (2018). Drug-Free Macromolecular Therapeutics Induce Apoptosis via Calcium Influx and Mitochondrial Signaling Pathway. Macromolecular bioscience, 18(1),
  51. Zhang R, Yang J, Radford DC, Fang Y, Kope'ek (2017). FRET Imaging of Enzyme-Responsive HPMA Copolymer Conjugate. Macromolecular bioscience, 17(1),
  52. Krimmer SG, Pan H, Liu J, Yang J, Kope'ek (2011). Synthesis and characterization of poly(¿-caprolactone)-block-poly[N-(2-hydroxypropyl)methacrylamide] micelles for drug delivery. Macromolecular bioscience, 11(8), 1041-51.
  53. Gao SQ, Sun Y, Kopecková P, Peterson CM, Kopecek (2009). Antitumor efficacy of colon-specific HPMA copolymer/9-aminocamptothecin conjugates in mice bearing human-colon carcinoma xenografts. Macromolecular bioscience, 9(11), 1135-42.
  54. Pan H, Sima M, Yang J, Kope'ek (2013). Synthesis of long-circulating, backbone degradable HPMA copolymer-doxorubicin conjugates and evaluation of molecular-weight-dependent antitumor efficacy. Macromolecular bioscience, 13(2), 155-60.
  55. Fowers KD, Kope'ek (2012). Targeting of multidrug-resistant human ovarian carcinoma cells with anti-P-glycoprotein antibody conjugates. Macromolecular bioscience, 12(4), 502-14.
  56. Liu J, Kope'ková P, Pan H, Sima M, Bühler P, Wolf P, Elsässer-Beile U, Kope'ek (2012). Prostate-cancer-targeted N-(2-hydroxypropyl)methacrylamide copolymer/docetaxel conjugates. Macromolecular bioscience, 12(3), 412-22.
  57. Yang J, Jacobsen MT, Pan H, Kopecek (2010). Synthesis and characterization of enzymatically degradable PEG-based peptide-containing hydrogels. Macromolecular bioscience, 10(4), 445-54.
  58. Pan H, Liu J, Dong Y, Sima M, Kopecková P, Brandi ML, Kopecek (2008). Release of prostaglandin E(1) from N-(2-hydroxypropyl)methacrylamide copolymer conjugates by bone cells. Macromolecular bioscience, 8(7), 599-605.
  59. Cuchelkar V, Kopecková P, Kopecek (2008). Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates. Macromolecular bioscience, 8(5), 375-83.
  60. Wang J, Li L, Yang J, Clair PM, Glenn MJ, Stephens DM, Radford DC, Kosak KM, Deininger MW, Shami PJ, Kope'ek (2019). Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine. Nanomedicine, 16, 217-225.
  61. Kopecek J, Yang (2009). Peptide-directed self-assembly of hydrogels. Acta biomaterialia, 5(3), 805-16.
  62. Segal E, Pan H, Ofek P, Udagawa T, Kopecková P, Kopecek J, Satchi-Fainaro (2009). Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PloS one, 4(4), e5233.
  63. Low SA, Galliford CV, Jones-Hall YL, Roy J, Yang J, Low PS, Kope'ek (2017). Healing efficacy of fracture-targeted GSK3ß inhibitor-loaded micelles for improved fracture repair. Nanomedicine (London, England), 12(3), 185-193.
  64. Kope'ek J, Stanwix (2014). Interview with Professor Jind'ich Kope'ek. Nanomedicine (London, England), 9(5), 577-9.
  65. Pelaz B, Alexiou C, Alvarez-Puebla RA, Alves F, Andrews AM, Ashraf S, Balogh LP, Ballerini L, Bestetti A, Brendel C, Bosi S, Carril M, Chan WC, Chen C, Chen X, Chen X, Cheng Z, Cui D, Du J, Dullin C, Escudero A, Feliu N, Gao M, George M, Gogotsi Y, Grünweller A, Gu Z, Halas NJ, Hampp N, Hartmann RK, Hersam MC, Hunziker P, Jian J, Jiang X, Jungebluth P, Kadhiresan P, Kataoka K, Khademhosseini A, Kope'ek J, Kotov NA, Krug HF, Lee DS, Lehr CM, Leong KW, Liang XJ, Ling Lim M, Liz-Marzán LM, Ma X, Macchiarini P, Meng H, Möhwald H, Mulvaney P, Nel AE, Nie S, Nordlander P, Okano T, Oliveira J, Park TH, Penner RM, Prato M, Puntes V, Rotello VM, Samarakoon A, Schaak RE, Shen Y, Sjöqvist S, Skirtach AG, Soliman MG, Stevens MM, Sung HW, Tang BZ, Tietze R, Udugama BN, VanEpps JS, Weil T, Weiss PS, Willner I, Wu Y, Yang L, Yue Z, Zhang Q, Zhang Q, Zhang XE, Zhao Y, Zhou X, Parak W (2017). Diverse Applications of Nanomedicine. ACS nano, 11(3), 2313-2381.
  66. Chu TW, Yang J, Zhang R, Sima M, Kope'ek (2014). Cell surface self-assembly of hybrid nanoconjugates via oligonucleotide hybridization induces apoptosis. ACS nano, 8(1), 719-30.
  67. Yang J, Kope'ek (2017). The Light at the End of the Tunnel-Second Generation HPMA Conjugates for Cancer Treatment. Current opinion in colloid & interface science, 31, 30-42.
  68. Kope'ek (2009). HYDROGELS FROM SOFT CONTACT LENSES AND IMPLANTS TO SELF-ASSEMBLED NANOMATERIALS. Journal of polymer science. Part A, Polymer chemistry, 47(22), 5929-5946.
  69. Yang J, Luo K, Pan H, Kope'ková P, Kope'ek (2011). Synthesis of Biodegradable Multiblock Copolymers by Click Coupling of RAFT-Generated HeterotelechelicPolyHPMA Conjugates. Reactive & functional polymers, 71(3), 294-302.
  70. Yang J, Kope'ek (2015). POLYMERIC BIOMATERIALS AND NANOMEDICINES. Journal of drug delivery science and technology, 30(Pt B), 318-330.
  71. Chu TW, Kosak KM, Shami PJ, Kope'ek (2014). Drug-free macromolecular therapeutics induce apoptosis of patient chronic lymphocytic leukemia cells. Drug delivery and translational research, 4(5-6), 389-94.
  72. Peng ZH, Kope'ek (2014). HPMA Copolymer CXCR4 Antagonist Conjugates Substantially Inhibited the Migration of Prostate Cancer Cells. ACS macro letters, 3(12), 1240-1243.
  73. Zhang R, Yang J, Chu TW, Hartley JM, Kope'ek (2015). Multimodality imaging of coiled-coil mediated self-assembly in a "drug-free" therapeutic system. Advanced healthcare materials, 4(7), 1054-65.

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