Difluoroboron curcumin/glycyrrhizic acid liposome-incorporated Mg²⁺-chelated microgel for MRSA-infected wound photothermal therapy.

AIMS: Photothermal therapy shows potential for treating wound infection, but unstable agents and possible tissue damage limit its use. We aimed to develop a strategy that removes Methicillin-resistant Staphylococcus aureus (MRSA) and supports wound healing.

METHODS

After confirming the stable photothermal activity of difluoroboron-curcumin (DF-Cur), we prepared a Mg2+-chelated microgel via microfluidics that co-delivers DF-Cur and glycyrrhizic acid (GA) within liposomes (termed GD Lip@Mg). And then its photothermal performance and in vitro and in vivo antibacterial ability were systematically examined. We evaluated the therapeutic efficacy of GD Lip@Mg in MRSA-infected full-thickness wounds in both rat and pig model, as well as exploring the underlying mechanisms.

RESULTS

Proteomic analysis revealed that GA inhibits the bacterial stress-response chaperone HSP60, thereby directly sensitizing MRSA to DF-Cur-mediated photothermal killing. GD Lip@Mg plus 450 nm laser reduced bacterial counts by > 99.9 %, increased re-epithelialization, collagen deposition and vessel density, and shifted macrophages from M1 to M2 without thermal damage. Transcriptomic data associated these effects with photothermal-induced up-regulation of nerve growth factor (NGF) and down-regulation of matrix metalloproteinases (MMPs).

CONCLUSIONS

GD Lip@Mg combined with laser decreases MRSA load and promotes wound healing, providing a translatable approach for infected wounds caused by resistant bacteria.