Two birds with one stone: Charge flip assisted colon-targeting hybrid nanoplatform for both drug delivery and...

Sweeping proinflammatory factors has shown critical potential for curing inflammatory diseases. Hence, it is promising to explore a synergistic strategy combining colon-targeting drug delivery and proinflammatory factor scavenging for better management of inflammatory bowel disease (IBD). Herein, we constructed a colon-targeting nanoplatform by hybridizing an inorganic carrier, mesoporous silica nanoparticle (MSN) with an organic cationic functional polymer polyethyleneimine (PEI), and an anionic coating, Eudragit. The resultant nanoplatform exhibits uniform size, improved drug loading, on-demand drug release, and effective colon-targeting and retention capabilities via surface charge flip. Importantly, it can selectively release the loaded aminosalicylate prodrug olsalazine sodium (OLZ) in simulated colonic fluid while regulating macrophage polarization by binding and scavenging proinflammatory anionic cfDNA through electrostatic interaction with the exposed cationic PEI. Meanwhile, it alleviates the mucosal barrier damage of intestinal epithelial cells. Benefiting from its satisfactory attributes, this nanoplatform has been successfully applied in the treatment of colitis in a mouse model, demonstrating a significant protective effect on the intestinal mucosa. These results confirmed that it is promising for better IBD management to employ the synergistic intervention strategy integrating colon-targeting drug therapy and proinflammatory cfDNA scavenging.