Self‐Assembled HYP Liposome Nanoparticles Promote Diabetic Wound Healing by Regulating the Polarization of M1 Macrophages

Abstract Suppression of the polarization of M1 macrophages is crucial for promoting diabetic wound healing. Hypahorine (HYP), a small molecule alkaloid compound with anti‐inflammatory properties, is encapsulated in liposome nanospheres (HYP‐INPS) using a one‐step ultrasound method and applied to treat open wounds in diabetic rats. Transmission electron microscopy (TEM) revealed that HYP‐INPS nanoparticles are spherical and coated with a lipid layer. ZetaPALS analysis demonstrated that HYP‐INPS has a potential of ‐15.67 ± 2.58 mV and a size of 212.87 ± 13.34 nm. In vitro, confocal microscopy revealed the cellular uptake of HYP‐INPS in macrophages. Flow cytometry showed that HYP‐INPS inhibited the polarization of bone marrow‐derived macrophages (BMDMs) to the M1 phenotype. In vivo, HYP‐INPS promoted diabetic wound healing by improving the inflammatory microenvironment within wounds. Immunofluorescence revealed that HYP‐INPS up‐regulated the expression of M2 macrophages and down‐regulated the expression of M1 macrophages at the wound site. Transcriptome sequencing showed that HYP‐INPS treatment specifically up‐regulated ASB10 expression in LPS‐induced RAW264.7 cells. Loss‐of‐function or gain‐of‐function experiments confirmed the regulatory role of ASB10 in M1 macrophage polarization. Therefore, HYP‐INPS targeted ASB10 is concluded to accelerate wound healing in diabetes by inhibiting the polarization of M1 macrophages and improving the inflammatory microenvironment. This newly developed HYP‐INPS system holds promise as a potential treatment for diabetic wounds.