Extracellular protease activation of chemotherapeutics from hydrogel matrices: a new paradigm for local chemotherapy.

A novel paradigm for local cancer chemotherapy, based upon local activation of chemotherapeutic molecules by soluble proteases, is presented. In the presence of matrix metalloproteases, a family of cancer-associated proteases, cisplatin is released from a hydrogel matrix in an active form. In the absence of matrix metalloproteases, cisplatin is released at a much lower rate. The mesh size of the polymer controls metalloprotease-based cisplatin release from the hydrogel matrix with approximate doubling of cisplatin release in the presence of matrix metalloprotease. Overall, this novel paradigm shows much potential for local chemotherapy where local chemotherapeutic release is in response to the invasive properties of the tumor. Keywords: Prodrug; cancer; chemotherapy; hydrogel; drug activation; targeted delivery; drug delivery