Ruthenium-quercetin coordinated nanotherapeutics with macrophage polarization regulation to rapidly promote bacterial-infected wound healing

Abstract

The hypoxic and inflammatory microenvironment induced by bacterial invasion of wound tissue severely hinders the healing process. In recent years, photothermal therapy (PTT) based on metal–polyphenol coordination networks has garnered considerable attention due to its potent antibacterial effects, biofilm-disrupting capabilities, and intrinsic enzyme-like activities. In this study, a metal–polyphenol coordinated nanotherapeutic system was constructed via synergistic coordination-driven self-assembly between the transition metal ruthenium and quercetin (referred to as QRs). These QRs demonstrated excellent photothermal conversion efficiency and antibacterial performance, while also catalyzing the decomposition of hydrogen peroxide into oxygen under inflammatory conditions. In an in vitro LPS-stimulated hypoxic macrophage model, treatment with QRs significantly reduced intracellular reactive oxygen species (ROS) levels and alleviated hypoxia, thereby downregulating hypoxia-inducible factor-1α (HIF-1α) expression and promoting macrophage polarization from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. In a murine bacterial wound infection model, QRs effectively suppressed the expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while enhancing endothelial cell proliferation and increasing the proportion of M2 macrophages at the wound site. These changes collectively facilitated the timely transition of the wound into the remodeling phase and maximized the regenerative potential of endogenous immune cells. Overall, this work highlights the potential of ruthenium-based materials for photothermal antibacterial therapy and proposes a promising strategy to remodel the wound microenvironment for enhanced tissue repair.