2D is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti-inflammatory Capability

Polydopamine nanomaterials have emerged as one of the most popular organic materials for management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfied because of limited phenolic hydroxyl groups and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, we reported two-dimension (2D) cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibited 3∼4-fold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules were absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms revealed that cationic PDA NSs could concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviated the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid. This article is protected by copyright. All rights reserved