Polymeric micelle-based hydrogen sulfide donors

Statement of Purpose: Hydrogen sulfide (H₂S) serves as a gaseous signal-transmitter molecule in the human body that regulates inflammation, relaxes vascular smooth muscles, promotes angiogenesis and mediates neurotransmission. With the discovery of the biological significance of H₂S, the potential for H₂S-based therapies has attracted growing attention. However, due to its volatile nature and a short half-life under physiological conditions, development of H₂S delivery systems, which enables the release of H₂S at the site of interest in a controlled manner are needed in order to explore its full therapeutic potential. One common approach is to use H₂S donor compounds, such as anethole dithiolethione (ADT) derivatives, which generate H₂S under physiological conditions. However, the fast and uncontrolled rate of H₂S release, toxic side effects of the donor compounds and/or their decomposition byproducts as well as rapid renal clearance remain as the major problems associated with the use of small H₂S donor compounds. To address this issue, we developed nano-sized gas donors based on polymeric micelles (H₂S donor micelles, Figure 1) which enable sustained H₂S release under physiological conditions. Here, we report design, synthesis and characterization of polymeric H₂S donor micelles containing anethole dithiolethione (ADT) moieties. Furthermore, the anti-cancer activities of these micelles were evaluated in the in vitro cell culture assays as well as the in ovo chick chorioallantoic membrane (CAM) assay.