On-demand release of CO in dual-responsive nanocomposite hydrogels for wound dressing

Gaseous signaling molecules, especially carbon monoxide (CO), hold promising potential for disease management. The therapeutic efficacy of CO is closely tied to its concentration, however, maintaining it at optimal levels for both efficacy and safety is highly challenging. To address this, we designed a dual-responsive (pH/red light) nanocomposite hydrogel for on-demand CO release. We first synthesized a hybrid nanocomposite (CaCO₃@AgCCN) comprising a CO₂ donor (CaCO₃) and a photocatalyst (Ag₃PO₄-decorated carbon dot g-C₃N₄, AgCCN) capable of converting CO₂ to CO. The size of CaCO₃ particles was approximately 40 nm, while that of AgCCN was around 150 nm in this nanocomposite. CaCO₃@AgCCN was then incorporated into chitosan (CS) to form a nanocomposite hydrogel. This nanocomposite hydrogel could respond to a mildly acidic environment due to bacterial growth, generating CO₂ exactly where it is needed (the wound site), which would be subsequently catalytically converted to CO by AgCCN under 630-nm red light illumination to facilitate wound healing. The generated CO, readily controlled by adjusting the CaCO₃@AgCCN content in the nanocomposite hydrogel and the red-light illumination time (the CO concentration reaching 4.7 μM after 10-min illumination), has demonstrated strong bactericidal and anti-inflammatory effects, both essential in facilitating wound healing as shown in both in vitro and in vivo studies. Coupled with satisfactory biocompatibility, this dual-responsive nanocomposite hydrogel appears to hold great promise for safe and effective applications of CO in biomedical fields.