Neutrophil Airfreighter Efficiently Delivers siRNA‐Loaded Nanocomplex to Mononuclear Phagocytes for Inhibition of mtDNA‐Induced Inflammation

Abstract The extensive intercellular material and information flow in the immune microenvironment is instructive to the development of targeted delivery strategies, but has received little attention previously. In this study, efferocytosis, an important link of material and information flow during inflammation, is creatively used to achieve a significant increase of targeted delivery efficiency. A tailored “neutrophil airfreighter” strategy is developed to deliver plenty of siRNA‐loaded nanocomplexes (FCM@siNPs) to mtDNA‐releasing sentinel mononuclear phagocytes (MPs) in vivo, providing them with immuno‐directed information. FCM@siNPs consist of siRNA‐loaded mesoporous silicon modified with engineered NIH3T3 cell membranes. Based on this innovative strategy, the delivery efficiency of FCM@siNPs to MPs is improved by 360% in vitro and 120% in vivo. FCM@siNPs could effectively inhibit periodontal inflammation in mice by precisely regulating the mtDNA‐induced inflammatory response in MPs. This study suggests the potential of the organismal material and information flow in the design of efficient targeted delivery strategies.