Strontium-Luteolin Nanoparticles Promote M2 Macrophage Polarization and Accelerate Acute Wound Healing via Immune Microenvironment Regulation

Precise spatiotemporal control of inflammation serves as an effective means to regulate the inflammatory microenvironment and promote wound healing. This study constructed strontium‒luteolin (Sr‒Lut) nanoparticles with a spherical morphology, which demonstrated outstanding radical scavenging capacity through synergistic metal‒ligand effects. Specifically, Sr-Lut efficiently scavenges reactive oxygen species, inhibits the TNF-α/NF-κB and JAK-STAT signaling pathways, promotes M2 polarization, and simultaneously reduces the proinflammatory factor IL-1β and increases the anti-inflammatory factor IL-10. Transcriptomic analysis revealed that Sr-Lut reprogrammed macrophages to downregulate Ccl4 and Retnlg while upregulating extracellular matrix remodeling-associated genes. In vivo experiments demonstrated that Sr-Lut accelerated wound closure in a dose-dependent manner, achieving a healing rate of 94.33% by day 11, which was significantly greater than the 58.54% reported in the control group, while also enhancing re-epithelialization and collagen deposition. Wound tissue RNA sequencing revealed that Sr-Lut inhibits the IL-17, Toll-like receptor and NF-κB signaling pathways while promoting the expression of genes associated with epidermal structural components. In summary, a dual-function nanocomposite with both anti-inflammatory and tissue-repair capabilities has been developed, offering a promising immunomodulatory strategy for wound treatment.