Multifunctional photothermal-driven PEG-grafted/CuS-loaded dendritic mesoporous organosilicon nanomotors for accelerated wound healing

Infected wounds pose a significant challenge to healing due to bacterial biofilms and persistent inflammation, which conventional therapies often fail to address effectively. To overcome these limitations, this study introduces multifunctional thermophoretic nanomotors (PDC NMs) for the synergistic treatment of infected wounds. The PDC NMs were engineered using dendritic mesoporous organosilicon carriers with tetrasulfide bonds and surface-loaded copper sulfide nanoparticles (CuS NPs). The tetrasulfide bonds enable the glutathione (GSH)-responsive release of hydrogen sulfide (H 2 S). At the same time, the CuS nanoparticles facilitate near-infrared (NIR) light-driven photothermal therapy (PTT) and propulsion, allowing deep biofilm penetration and disruption. Polyethylene glycol (PEG) modification further enhances biocompatibility and colloidal stability. In vitro and in vivo experiments demonstrate that PDC NMs effectively reduce wound size, bacterial survival, and inflammation while promoting angiogenesis, collagen synthesis, and hair regrowth. Notably, by day 9, PDC NMs + NIR treatment achieved an 87.67 ± 1.55 % reduction in wound area and an 85.80 ± 0.23 % decrease in bacterial survival compared to the control groups. Additionally, PDC NMs modulate macrophage polarization from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype, suppress the expression of pro-inflammatory cytokines (IL-6 and TNF-α), and enhance anti-inflammatory responses (IL-10). Biocompatibility and organ toxicity evaluations confirmed minimal hemolysis (<5 %), normal liver and kidney function, and no histological damage to major organs, ensuring the biosafety of PDC NMs. By combining PTT, H 2 S gas therapy, and GSH depletion, PDC NMs offer an antibiotic-free, biocompatible approach to treating biofilm-associated wound infections. This innovative strategy provides a promising alternative to conventional antibiotics, addressing both infection control and tissue regeneration in wound healing. • PDC NMs exhibit asymmetric structure via Pickering emulsions. • PDC NMs combine photothermal therapy, deplete GSH, and release controlled H 2 S. • PDC NMs penetrate biofilms via self-thermophoresis, effectively eradicating bacteria. • In vivo studies show reduced inflammation, accelerated angiogenesis, and enhanced wound healing. • This antibiotic-free approach offers a promising alternative to conventional antibiotics.