Platelet-inspired nanomedicine targeting activated neutrophils to alleviate ulcerative colitis by free radicals scavenging and controlled neutrophil swarming

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that causes inflammation and ulcers in the intestinal tract. Current therapies focus on the relief of symptoms in the short-term while it is an urgent need to achieve long-term remission of inflammation in clinics. In the current study, Platinum-doped carbon nanodot (CD) nanozymes (PtCD) with cascade enzymatic activities for superoxide dismutase/catalase (SOD/CAT) were successfully synthesized. PtCD and spleen tyrosine kinase (SYK) inhibitor piceatannol were co-loaded in PLGA and coated with platelet membrane to form a platelet-inspired nanomedicine (PM@Pic/PtCD@NP). PtCD-loaded nanoparticles (PtCD@NP) were found to co-locate with mitochondria, scavenge reactive oxygen species (ROS), and reduce the expression of pro-inflammatory cytokines. In addition, the biomimetic modification with the platelet membrane enabled PM@Pic/PtCD@NP to hitchhike neutrophils to the site of inflammation and release piceatannol to inhibit neutrophil swarming. Intravenous administration of PM@Pic/PtCD@NP partially reversed and prevented intestinal inflammation and intestinal barrier dysfunction in a murine model of colitis. The RNA-sequencing analysis revealed that gene markers of mitochondrial respiratory chain complex Ⅰ were significantly associated with PM@Pic/PtCD@NP treatment. Collectively, This study suggests that PM@Pic/PtCD@NP treatment may serve as an innovative therapeutic strategy for the long-term remission of UC.