A macromolecular prodrug of doxorubicin conjugated to a biodegradable cyclotriphosphazene bearing a tetrapeptide.

A new biodegradable water-soluble phosphazene trimer-doxorubicin conjugate was synthesized, in which equimolar hydrophilic methoxy-poly(ethylene glycol) with a molecular weight of 350 (MPEG350) and a tumor-specific tetrapeptide (Gly-Phe-Leu-Gly) were grafted to cyclotriphosphazene. The present conjugate exhibited cytotoxicity lower than that of free doxorubicin (IC50=0.10 microM) but a reasonably higher in vitro cytotoxicity (IC50=1.1 microM) against the leukemia L1210 cell line probably due to its enzymatically controlled release.