A Novel Catalase Nanogels for Effective Treatment of Neutrophilic Asthma

Neutrophilic asthma, as corticosteroid resistant asthma, is clinically more severe than eosinophilic asthma. Therefore, the treatment of neutrophilic asthma has been a challenging. Reactive oxygen species (ROS) play a key role in the neutrophilic asthma. However, the direct use of antioxidant enzymes, such as catalase (CAT), is challenging due to the poor stability, short plasma half-life, and the lack of effective drug delivery systems to pulmonary systems. In this work, a novel kind of nanogels for delivering CAT (CAT-NGs) is synthesized, incorporating CAT with an antibacterial "protective film", as a modality for the treatment of neutrophilic asthma. Compared with free CAT, CAT-NGs demonstrated superior enzyme activity and trypsin resistance, and exhibited outstanding anti-inflammatory and antioxidant activities in vitro. Furthermore, CAT-NGs showed significant inhibitory effects on nontypeable Haemophilus influenzae (NTHi), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Additionally, nebulized inhalation of CAT-NGs alleviated pulmonary inflammation in neutrophilic asthma mice. Mechanistically, the alleviation of neutrophilic asthma symptoms by CAT-NGs is possibly associated with the clearance of ROS in the lung and the inhibition of the NLRP3 and NF-kappa B pathways. Hence, the work have demonstrated the therapeutic potential of CAT-NGs, offering new insights into the clinical treatment of neutrophilic asthma.