Polymeric conjugates based on HPMA copolymers
In collaboration with the Department of Biomedical Polymers at the Institute of Macromolecular Chemistry, we are developing polymeric conjugates based on HPMA copolymers that carry the chemotherapeutic drugs gemcitabine or docetaxel. These drugs are covalently bound to the HPMA copolymer carrier through a defined chemical bond using an appropriately chosen linker. The nature of the chemical bond (either an enzymatically degradable amide or a pH-sensitive hydrazone bond) and the linker between the drug and the polymer carrier determine the conditions and kinetics of the drug’s release back into its pharmacologically active form.
This is a critical parameter that plays a fundamental role in the toxicity and antitumor efficacy of these polymer conjugates. We are testing gemcitabine and docetaxel conjugates for their in vitro and in vivo antitumor activity in appropriately selected mouse and human tumor models. These conjugates show promising potential for treating pancreatic, breast, lung, and head and neck cancers.
Immunogenic cell death of tumor cells
We are also developing similar polymer conjugates carrying mitoxantrone derivatives, expected to retain mitoxantrone’s ability to effectively induce immunogenic cell death of tumor cells. This should enable effective combination of these conjugates with immunotherapeutic approaches aimed at stimulating T lymphocytes. These conjugates are being tested in models of androgen-independent prostate cancer and acute myeloid leukemia.
