NIR-responsive prussian Blue/Fer-1 co-loaded nanozymes for synergistic therapy of acute lung injury

Sepsis-associated acute lung injury (ALI) is a critical clinical problem owing to the complex interactions between inflammation and oxidative stress. It is often associated with high mortality rates and a lack of therapeutic options. To simultaneously combat the interconnected inflammatory and oxidative stress pathways in sepsis-associated ALI, we designed near-infrared (NIR)-responsive nanomedicine by co-loading ferroptosis inhibitor Ferrostatin-1 (Fer-1) with Prussian blue nanozymes (denoted as Fer-1@PB) to achieve synergistic therapy and enhanced efficacy. Fer-1@PB combines the multi-enzyme mimetic properties of PB nanoparticle-based nanozyme (PBzyme) for reactive oxygen species (ROS) scavenging and the ferroptosis-inhibitory function of Fer-1 with spatiotemporally controlled burst release under NIR irradiation. The 0.05), and the conclusion of colloidal stability remains completely unchanged. All the above revisions are limited to typographical adjustments, wording accuracy, and minor typo corrections. No experimental data, results, figures, or cistance. Sincerely, Xiaoran Liu (on behalf of all authors) Corresponding author"?> Fer-1@PB nanozymes exhibited strong therapeutic efficacy in cellular and animal sepsis-related ALI models, with an increased survival rate, reduced pulmonary edema and histopathological damage, and recovery of lung function. Mechanistic investigations using transcriptomic analysis (RNA-seq) and experimental validation revealed that the therapeutic effects were mediated by the modulation of the CXCL2/ARF6/NCF1 signaling axis. This study introduces Fer-1@PB as a highly efficient and biosafe nanotherapeutic approach for ALI via synergistic anti-oxidative and anti-inflammatory effects. It also outlines a new molecular mechanism of action, yielding new insights into the precise nanomedicine for inflammatory lung disease.