Apoptotic neutrophil membrane-modified nanoparticles promote wound healing by enhancing efferocytotic capacity of dendritic cells.

Chronic and large wound healing failures pose significant challenges in clinical practice. The major difficulty in wound healing concerns the limited efferocytic activity of dendritic cells (DCs). Focusing on the critical role of DCs efferocytosis in chronic wound healing, this study proposes a dual-pathway intervention strategy. Firstly, on the basis of the mechanism that SLC7A11 is abnormally highly expressed in diabetic wounds and inhibits the efferocytic activity of DCs, a novel inhibitor HG106 is utilized to target and inhibit SLC7A11, significantly enhancing the clearance efficiency of apoptotic cells by DCs. Secondly, inspired by the physiological apoptotic signals of neutrophils, an apoptotic neutrophil membrane (ANM)-modified liposome (HG106-ANM@Lip) is constructed. This enhances the recognition and uptake of nanoparticles by DCs through the surface phosphatidylserine (PS) signal and synergistically activates the MERTK/AXL receptor pathway to initiate and enhance efferocytosis, improving the inflammatory microenvironment. In diabetic mice and a large wound model of Bama pigs, HG106-ANM@Lip demonstrates a good promoting effect on wound healing. In summary, this study presents an innovative synergistic strategy for chronic wound treatment, utilizing the dual mechanisms of molecular regulation and biomimetic delivery to reshape the inflammatory microenvironment.