Abstract
Hydrogen sulfide (H₂S) imbalance has been implicated in pathologies, and reinstating H₂S homeostasis could be a useful therapeutic strategy. However, delivery of H₂S to the disease site remains a challenge. Functionalised nanoformulations could be used as a strategy to deliver high concentrations of H₂S in a targeted manner. Use of a disease-associated trigger that activates and releases H₂S would provide therapeutic selectivity. As proof-of-concept, synthesis and formulation of block co-polymers bearing a thiocarbamate bond, a carbonyl sulfide (COS) precursor, is described. Activation by hydrogen peroxide (H₂O₂), and a subsequent 1,6-self-immolation process leads to release of COS, which in the presence of carbonic anhydrase is hydrolysed to H₂S. H₂S generation was exemplified by reduction of an azido-pro-fluorophore. Formulation of the polymer resulted in compound vesicles that were able to encapsulate a model drug and could be useful in future biological studies exploring delivery of H₂S as a therapeutic, or to activate azido-masked prodrug/pro-fluorophore in areas of high reactive oxygen species (ROS).