H-gemcitabine: a new gemcitabine prodrug for treating cancer.

In this report, we present a new strategy for targeting chemotherapeutics to tumors, based on targeting extracellular DNA. A gemcitabine prodrug was synthesized, termed H-gemcitabine, which is composed of Hoechst conjugated to gemcitabine. H-gemcitabine has low toxicity because it is membrane-impermeable; however, it still has high tumor efficacy because of its ability to target gemcitabine to E-DNA in tumors. We demonstrate here that H-gemcitabine has a wider therapeutic window than free gemcitabine.