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

作　　者：Jiajun Cai Hui Tao Huan Liu Yi Hu Songling Han Wendan Pu Lanlan Li Gang Li Chenwen Li Jianxiang Zhang 

机构地区：[1]Department of Pharmaceutics,College of Pharmacy,Third Military Medical University(Army Medical University),Chongqing,400038,PR China [2]Department of Pharmacology,College of Pharmacy,Third Military Medical University(Army Medical University),Chongqing,400038,PR China [3]State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University(Army Medical University),Chongqing,400038,PR China [4]Department of Pharmaceutical Analysis,College of Pharmacy,Third Military Medical University(Army Medical University),Chongqing,400038,PR China

出　　处：《Bioactive Materials》2023年第10期12-26,共15页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(Nos.81971727 and 32271451);the Program for Scientific and Technological Innovation Leader of Chongqing(No.CQYC20210302362);the Program for Distinguished Young Scholars of TMMU,and the Graduate Supervisor Team Program of Chongqing in 2022.

摘　　要：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 nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively 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 targeting 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 inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.

关 键 词：Neutrophilic asthma Nanotherapy Neutrophil extracellular traps INFLAMMASOME Precision therapy 

分 类 号：R562.25[医药卫生—呼吸系统]