Glucose oxidase triggers gelation of N-hydroxyimide-heparin conjugates to form enzyme-responsive hydrogels for cell-specific drug delivery

A new strategy for creating enzyme-responsive hydrogels by employing an N-hydroxyimide-heparin conjugate, designed to act as both an enzyme-mediated radical initiator and an enzyme-sensitive therapeutic carrier, is described. A novel enzyme-mediated redox initiation system involving glucose oxidase (GOx), an N-hydroxyimide-heparin conjugate and glucose is reported. The GOx-mediated radical polymerization reaction allows quick formation of hydrogels under mild conditions, with excellent flexibility in the modulation of the physical and chemical characteristics. The heparin-specific enzymatic cleavage reaction enables the delivery of cargo from the hydrogel in amounts that are controlled by the environmental levels of heparanase, which is frequently associated with tumor angiogenesis and metastasis. The formed hydrogels can realize cell-specific drug delivery by targeting cancer cells that are characterized by heparanase overexpression, whilst showing little toxicity towards normal cells.