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Journal of Bioactive and Compatible Polymers
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Polymer—Doxorubicin Conjugate with a Synthetic Peptide Ligand Targeted on Prostate Tumor

Robert Pola

Institute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic, pola{at}imc.cas.cz

Michal Pechar

Institute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic

Karel Ulbrich

Institute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic

Àngels Fabra Fres

Department of Cancer and Metastasis, Institut de Recerca Oncologica Hospital Duran y Reynals, Barcelona, Spain

In this study, the synthesis, physico-chemical characterization, and antiproliferative effects of a polymer—doxorubicin conjugate targeted by the amide of peptide sequence CPLHQRPMC are described. This sequence is discovered using the phage display method to achieve high affinity to prostate cancer cell line PC3MM2. The peptide is bound to N-(2-hydroxypropyl)methacrylamide-based copolymer carrier via a hydrophilic undeca(ethylene oxide) spacer. Doxorubicin is attached to the polymer using a pH-sensitive hydrazone bond which proves to be stable at a physiological pH 7.4 but quickly hydrolyzes at pH 5.0. The polymer—drug conjugate exhibits significant antiproliferative activity against human metastatic prostate cancer cell line PC3MM2 in vitro. The addition of a second polymer with the targeting peptide but without doxorubicin to the incubation media leads to a decrease in the cytotoxicity of 32% induced by the first polymer. This finding indicates a receptor-specific endocytosis of the polymeric drug.

Key Words: drug delivery systems • drug research • hydrazones • peptide targeting • polymers.

Journal of Bioactive and Compatible Polymers, Vol. 22, No. 6, 602-620 (2007)
DOI: 10.1177/0883911507084423
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