Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPG_A)-coated TiS₂ nanosheets (TLPG_A) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPG_A exhibited higher cfDNA affinity than the TiS₂ nanosheets coated with dendritic polyglycerol-amine (TDPG_A). TLPG_A reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPG_A displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.