Multifunctional Boron-based 2D Nanoplatforms Ameliorate Severe Respiratory Inflammation by Targeting Multiple Inflammatory Mediators.

Abstract

Effective management of serious respiratory diseases, such as asthma and recalcitrant rhinitis, remains a global challenge. Here, it is shown that induced sputum supernatants (ISS) from patients with asthma contain higher levels of cell-free DNA (cfDNA) compared to that of healthy volunteers. Although cfDNA scavenging strategies have been developed for inflammation modulation in previous studies, this fall short in clinical settings due to the excessive neutrophil extracellular trap (NET) formation, reactive oxygen and nitrogen species (RONS) and bacterial infections in injured airway tissues. Based on this, a multifunctional boron-based 2D nanoplatform B-P_M is designed by coating boron nanosheets (B-NS) with polyamidoamine generation 1 (PG1) dendrimer, which can simultaneously target cfDNA, NETs, RONS, and bacteria. The effects of B-P_M in promoting mucosal repair, reducing airway inflammation, and mucus production have been demonstrated in model mice, and the therapeutic effect is superior to dexamethasone. Furthermore, flow cytometry with clustering analysis and transcriptome analysis with RNA-sequencing are adopted to comprehensively evaluate the in vivo anti-inflammation therapeutic effects. These findings emphasize the significance of a multi-targeting strategy to modulate dysregulated inflammation and highlight multifunctional boron-based 2D nanoplatforms for the amelioration of respiratory inflammatory diseases.