Ginsenoside Rb1-loaded bionic nanoparticles alleviate sepsis-induced acute lung injury by reducing mitochondrial oxidative stress to inhibit macrophage PANoptosis

Cytokin storms play a key role in the pathogenesis of acute lung injury (ALI) caused by sepsis, in which pulmonary macrophage PANoptosis is involved. At present, the main treatment methods for sepsis-induced ALI are antibiotics and fluid resuscitation, but the efficacy of these methods is unsatisfactory enough; therefore, the development of new therapeutic methods is urgently needed. In this study, we developed a novel bionic nanoparticle (R@ZQC NPs) using ZIF-8 nanoparticles as a carrier, internally supported with ginsenoside Rb1, and externally coated with quaternated chitosan and a macrophage membrane layer by layer. The biomimetic nanoparticles controlled the release of Rb1, had good biocompatibility, strong antibacterial activity, and targeted the inhibition of pulmonary macrophage PANoptosis. In vitro and in vivo, R@ZQC NPs effectively inhibited the activity of Escherichia coli and reduced mitochondrial damage by activating the AMPK pathway, thus alleviating the inflammatory response and ameliorating sepsis-induced ALI. In summary, this study revealed the great potential of R@ZQC NPs for antimicrobial activity, targeted inhibition of macrophage PANoptosis and reduction of the inflammatory response and represents the first attempt of R@ZQC NPs in the treatment of sepsis-induced ALI. This study provides new therapeutic ideas and strategies for the clinical treatment of sepsis-induced ALI.