Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity

A novel class of anti-cancer therapeutics – polymeric conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug – is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in compa...

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Bibliographic Details
Published in:Journal of controlled release 2005-12, Vol.110 (1), p.119-129
Main Authors: Mrkvan, Tomas, Sirova, Milada, Etrych, Tomas, Chytil, Petr, Strohalm, Jiri, Plocova, Dana, Ulbrich, Karel, Rihova, Blanka
Format: Article
Language:English
Subjects:
Acrylamides - chemical synthesis
Acrylamides - pharmacology
Animals
Anti-cancer chemotherapy
Anti-tumor immunity
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Delayed-Action Preparations
Doxorubicin
Doxorubicin - analogs & derivatives
Doxorubicin - chemical synthesis
Doxorubicin - pharmacology
EL4 lymphoma
Galactosamine - chemical synthesis
Galactosamine - pharmacology
General pharmacology
HPMA copolymer conjugates
Humans
Hydrogen-Ion Concentration
Immunotherapy, Adoptive
Inhibitory Concentration 50
Injections, Subcutaneous
Medical sciences
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Neoplasms, Experimental - immunology
Neoplasms, Experimental - prevention & control
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polymethacrylic Acids - chemical synthesis
Polymethacrylic Acids - pharmacology
Spleen - cytology
Spleen - immunology
Spleen - transplantation
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Summary:A novel class of anti-cancer therapeutics – polymeric conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug – is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in comparison with low-molecular-weight drugs, the macromolecular therapeutics show decreased acute as well as delayed adverse side-toxicity. More importantly, the polymeric conjugates trigger the onset of specific anti-tumor immune response and this anti-tumor immunity can be transferred with splenocytes to naïve recipients. In other terms, chemotherapy based on conjugates of HPMA copolymer with doxorubicin possesses immunomodulating properties. This finding might also have wider implications for the management of relapsing tumors in human patients.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2005.09.028