In this presentation we present a new cancer drug targeting system, termedH-gemcitabine, which can upregulate the tumor receptor it targets and hasautocatalytic drug targeting properties.  H-gemcitabine is composed of the DNA binding agent Hoechst conjugated to gemcitabine. H-gemcitabineinitially targets tumors by binding extracellular DNA (E-DNA) via its Hoechst moiety, which is overproduced in tumors due to their necrotic core.  After localizing in tumors H-gemcitabine releases free gemcitabine, which diffuses into neighboring tumor cells and kills them, which triggers the release of more E-DNA.  Therefore on subsequentrounds of therapy increased levels of H-gemcitabine are targeted to the tumor, due to the cell killing from the previous rounds of H-gemcitabine therapy.  We show here that H-gemcitabine has autocatalytic drug targeting properties in tumor spheroids, and is significantly more effective than free gemcitabine at treating xenografted tumors in nude mice.  We anticipate numerous applications of H-gemcitabine, given its unique autocatalytic drug targeting ability.

Autocatalytic drug delivery vehicle based on targeting extracellular DNA

241st National Meeting (2011)

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