HPMA-Anticancer Drug Conjugates

  • B. Rihova
  • O. Hovorka
  • L. Kovar
  • M. Kovar
  • T. Mrkvan
  • M. Sirova
  • V. Subr
  • K. Ulbrich
Part of the Macromolecular Anticancer Therapeutics book series (CDD&D)


Homopolymer poly(HPMA) was originally developed as a blood expander “Duxon.” Later on, linear nondegradable HPMA copolymer of a molecular weight ∼25 kDa was used as the backbone to which drugs, mostly doxorubicin, were attached through different side chains and different covalent bonds. Homopolymer and copolymers are non-toxic, biocompatible, and non-immunogenic molecules. To increase their accumulation in solid tumors and achieve maximal EPR effect, branched and grafted high molecular weight derivatives were designed containing oligopeptidic cross-links which can be degraded by lysosomal enzymes. In addition, linear HPMA copolymers were synthesized to form high molecular weight supramolecular structures. To fulfill the requirements for active targeting, poly- and monoclonal antibodies, carbohydrates, lectins, growth hormones, cell-surface active proteins and peptides have been employed. Non-targeted and targeted polymer–drug derivatives based on HPMA have both cytostatic and immunostimulating activity. Their impressive anti-tumor effects most likely result from the combination of strong direct cytotoxicity and a systemic anticancer resistance regularly induced during the treatment.


Polymer Precursor Drug Conjugate Polymeric Conjugate Free Doxorubicin HPMA Copolymer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



antithymocyte globulin




7,8-dehydro-9,10-desacetyldoxorubicinone (doxorubicin derivative)


dendritic cell




(also called PK1), non-targeted HPMA conjugate containing doxorubicin bound via amide bond


B1 monoclonal antibody-targeted HPMA conjugate containing doxorubicin bound via amide bond


human immunoglobulin-targeted HPMA conjugate containing doxorubicin bound via amide bond


non-targeted HPMA conjugate containing doxorubicin bound via pH-sensitive hydrazone bond


enhanced permeability and retention


high mobility group box 1 protein




heat-shock protein


human immunoglobulin


lymphokine-activated killer


multidrug resistance


maximum tolerated dose


natural killer cell


see Dox–HPMAAM


galactosamine-targeted HPMA conjugate containing doxorubicin bound via amide bond


peanut agglutinin


toll-like receptor 4


wheat germ agglutinin



This work was supported by grants of the Academy of Sciences of the Czech Republic no. KAN 200200651, Grant Agency of the Academy of Science of the Czech Republic no. IAAX00500803, the Ministry of Education, Youth and Sports of the Czech Republic no. 1M0505, and Institutional Research Concept AV 02 50200510.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • B. Rihova
    • 1
  • O. Hovorka
    • 1
  • L. Kovar
    • 1
  • M. Kovar
    • 1
  • T. Mrkvan
    • 1
  • M. Sirova
    • 1
  • V. Subr
    • 2
  • K. Ulbrich
    • 2
  1. 1.Institute of Microbiology Academy of Sciences of the Czech Republic, v.v.iVidenskaCzech Republic
  2. 2.Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic, v.v.i., Heyrovsky sq. 2Prague 6Czech Republic

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