Abstract
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.
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