HPMA-Anticancer Drug Conjugates

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.