Red blood cell-mimicking liposomes loading curcumin promote diabetic wound healing.

The excessive inflammatory response is known to be a major challenge for diabetic wound healing, while bacteria secreted toxin, α-hemolysin (Hlα), was recently reported to prolong inflammation and delay diabetic wound healing. In this study, we designed a red blood cell membrane (RBCM)-mimicking liposome containing curcumin (named RC-Lip) for the treatment of diabetic wounds. RC-Lips were successfully fabricated using the thin film dispersion method, and the fusion of RBC membrane with the liposomal membrane was confirmed via surface protein analysis. RC-Lips efficiently adsorbed Hlα, thereby reducing the damage and pro-apoptotic effects of Hlα on keratinocytes. Furthermore, they remarkably facilitated liposome uptake into macrophages with advanced curcumin release and regulation of M2 macrophage polarization. In a diabetic mouse and infected wound model, RC-Lips treatment significantly promoted wound healing and re-epithelialization while downregulating interleukin-1β (IL-1β) and upregulating interleukin-10 (IL-10). In summary, the results showed that the spongiform RC-Lips effectively modulate the inflammatory response after adsorbing Hlα and regulating M2 macrophage polarization, leading to a significant promotion of wound healing in diabetic mice. Hence, this study provides a prospective strategy of efficiently mediating inflammatory response for diabetic wounds.