Peptide-directed HPMA copolymer-doxorubicin conjugates as targeted therapeutics for colorectal cancer

Eva Kopansky, Yosi Shamay, Ayelet David

    Research output: Contribution to journalArticlepeer-review

    27 Scopus citations


    Synthetic oligopeptides have emerged as a promising class of targeting ligands, providing a variety of choices for the construction of conjugates for desired ligand functionality. To explore the potential of short peptides as ligands for targeted delivery of macromolecular therapeutics for colorectal cancer (CRC), fluorescently labelled HPMA copolymersbearing either G3-C12 or GE11 for targeting galectin-3 and epidermal growth factor receptor (EGFR), respectivelywere synthesised and the mechanisms of their internalisation and subcellular fate in CRC cells were studied. The targetability of the G3-C12 bearing copolymers towards galectin-3 was further compared to that of galactose-containing copolymers. The resulting G3-C12-bearing conjugate actively and selectively targets CRC tumour cells over-expressing galectin-3 and exhibits superior targetability to galectin-3 when compared to the galactose-bearing copolymer. GE11 copolymer conjugate binds specifically and efficiently to EGFR over-expressing cells, thus mediating internalisation to a significantly higher extent relative the copolymer conjugated to a scrambled sequence peptide. We further incorporated doxorubicin (DOX) into GE11 bearing copolymer via an acid-labile hydrazone bond. The GE11-DOX copolymer conjugate demonstrated higher cytotoxicity toward EGFR over-expressing cells relative to the control non-targeted DOX conjugate. Altogether, our results show a proof of principle for the selective delivery of DOX to the target CRC cells.

    Original languageEnglish
    Pages (from-to)933-943
    Number of pages11
    JournalJournal of Drug Targeting
    Issue number10
    StatePublished - 1 Dec 2011


    • Colorectal cancer
    • Drug targeting
    • EGFR
    • G3-C12
    • GE11
    • Galectin-3
    • HPMA copolymer-drug conjugates

    ASJC Scopus subject areas

    • Pharmaceutical Science


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