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.