Core-Cross-Linking of Polymeric Micelles by Di-para-Substituted S-Aroylthiooximes as Linkers for Controlled H2S Release
ACS MACRO LETTERS(2022)
摘要
As one of the gasotransmitters, the therapeutic effects of hydrogen sulfide (H2S) were reported widespread in recent years. Considering the short physiological half-life and significant dose-dependent effects of H2S, it is vital to achieve controlled H2S delivery for biomedical applications. Polymeric micelles have been explored to regulate H2S 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 H2S releasing efficiency is usually unavoidable. To solve these problems, we develop di-para-substituted S-aroylthiooximes (p-diSATOs) as linkers, which integrated cross-linking of micelle core and conjugation of H2S 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 H2S 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 H2S 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.
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