Photothermal-Boosted Neutrophil-Mediated STING Inhibitor Delivery Platforms for Drug-Resistant Diabetic Wound Infections

Chronic diabetic wounds infected by drug-resistant bacteria face impaired healing due to persistent inflammation, microbial resistance, and failed tissue regeneration, posing a dire clinical challenge with limited therapeutic options. This study presents a neutrophil (NE)-mediated delivery platform (NEmPC) integrating mesoporous polydopamine nanoparticles (NPs) loaded with an STING inhibitor (C176) to treat drug-resistant diabetic wound infections. Leveraging neutrophils' innate chemotaxis, NEmPC achieves targeted delivery to inflammatory sites, where inflammation-triggered neutrophil extracellular traps release and near-infrared (NIR)-activated photothermal therapy (PTT) enable spatiotemporal drug deployment. In vitro and in vivo results demonstrate that NEmPC inhibits the STING signaling pathway, reprograms pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes, and enhances drug release and bactericidal effects via PTT. The platform synergistically addresses chronic inflammation, bacterial resistance, and impaired tissue regeneration, offering a precision therapeutic strategy for diabetic wounds with minimized systemic toxicity.