Core-Cross-Linking of Polymeric Micelles by Di- para -Substituted S -Aroylthiooximes as Linkers for Controlled H 2 S Release.

As one of the gasotransmitters, the therapeutic effects of hydrogen sulfide (H 2 S) were reported widespread in recent years. Considering the short physiological half-life and significant dose-dependent effects of H 2 S, it is vital to achieve controlled H 2 S delivery for biomedical applications. Polymeric micelles have been explored to regulate H 2 S delivery. However, the dilution-induced dissociation of micelles in physiological conditions limits their therapeutic effects. The circulation stability of polymeric micelles could be improved through core-cross-linking, but reduced H 2 S releasing efficiency is usually unavoidable. To solve these problems, we developed di- para -substituted S -aroylthiooximes ( p -diSATOs) as linkers, which integrated cross-linking of micelle core and conjugation of H 2 S donors through one simple reaction. Compared with SATO-bearing non-cross-linked micelle, the core-cross-linked micelle (CCM) prepared through this method exhibited initial rapid H 2 S release owing to the electron-withdrawing effect of p -diSATOs, and subsequently, a sustained release could last for a long period of time. Considering the characteristic H 2 S releasing behavior of CCM, it may accelerate wound healing through initial efficient and subsequent prolonged pro-healing effects. As a proof of concept, we explored the therapeutic potential of CCM using a murine burn wound model, which exhibited pro-healing effect on burn wounds.