The preparation and characterization of a novel polymeric drug-delivery system designed for bone targeting of antineoplastics is described. The system was based on biocompatible poly[N-(2-hydroxypropyl)methacrylamide] carrier containing hydroxybisphosphonate targeting moieties and the model radiotherapeutics I-125 or In-111 or the anticancer drug doxorubicin. The in vitro binding studies with hydroxyapatite as a bone model proved that the system was efficiently adsorbed on this mineral. The systems contained model drugs bound by stable (amide), hydrolytically cleavable (hydrazone) or enzymatically cleavable (Gly-Phe-Leu-Gly tetrapeptide) spacers. It was proven in vitro that, in the case of cleavable spacers, the drug could be released from the polymer carrier at a rate depending on the pH or enzymatic stimulus. 2006 Wiley Periodicals, Inc.