Hydrogen sulfide-releasing micelles for promoting angiogenesis

Hydrogen sulfide (H2S), an important gaseous signalling molecule in the human body, has been shown to be involved in many physiological processes such as angiogenesis. Since the biological activities of H2S are known to be significantly affected by the dose and exposure duration, the development of H2S delivery systems that enable control of H2S release is critical for exploring its therapeutic potential. Here, we prepared polymeric micelles with different H2S release profiles, which were prepared from amphiphilic block copolymers consisting of a hydrophilic poly(N-acryloyl morpholine) segment and a hydrophobic segment containing H2S-releasing anethole dithiolethione (ADT) groups. The thermodynamic stability of the micelles was modulated by altering the ADT content of the polymers. The micelles with higher thermodynamic stability showed significantly slower H2S release. Furthermore, the sustained H2S release from the micelles enhanced migration and tube formation in human umbilical vein cells (HUVECs) and induced vascularlization in the in ovo chick chorioallantoic membrane (CAM) assay.