Intrinsically bioactive and biomimetic nanoparticle-derived therapies alleviate asthma by regulating multiple pathological cells

Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nano -therapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effec-tively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced tar-geting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflam-mation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Conse-quently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.

Automated summary

Asthma is a serious global health concern. A nanotherapy called LaCD NP, based on a cyclic oligosaccharide-derived bioactive material, has been developed to simultaneously regulate multiple target cells related to neutrophilic asthma. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells, reducing inflammation and improving asthmatic symptoms. The nanotherapy also showed good safety performance and promising potential for treating neutrophilic asthma and other neutrophil-associated diseases.