A DNA-based nanorobot for targeting, hitchhiking, and regulating neutrophils to enhance sepsis therapy

Targeted regulation of neutrophils is an effective approach for treating neutrophil-driven inflammatory diseases, but challenges remain in minimizing off-target effects and extending drug half-life. A DNA-based nanorobot was developed to target neutrophils by using an N-acetyl Pro-Gly-Pro (Ac-PGP) peptide to specifically bind to the C-X-C motif of chemokine receptor 2 (CXCR2) on neutrophil membranes. This robot (a tetrahedral framework nucleic acid modified with Ac-PGP, APT) identified and hitchhiked neutrophils to accumulate at inflammatory sites and prolong its half-lives, whilst also was internalized to influence the neutrophil cell cycle and maturation process to regulate oxidative stress, inflammation, migration, and recruitment in both in vivo and in vitro inflammation experiments. Consequently, the tissue damage caused by sepsis was greatly reduced. This novel neutrophil-based nanorobot highlights the high precision of targeting and regulating neutrophils, and presents a potential strategy for treating multiple neutrophil-driven diseases.