Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, () and (). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates , suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.

中文翻译：

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一种抗菌、多功能纳米凝胶，可有效治疗中性粒细胞性哮喘


哮喘是一种影响肺部和呼吸道的慢性异质性疾病。特别是，中性粒细胞亚型哮喘被描述为持续性、更严重且对皮质类固醇具有抵抗力。越来越多的证据表明，不可分型（NTHi）感染会导致中性粒细胞性哮喘的发生，加剧临床症状并增加相关的医疗负担。在这项工作中，精氨酸接枝壳聚糖（CS-Arg）与三（2-羧乙基）膦（TCEP）和高效抗菌剂聚-ε-L-赖氨酸（ε-PLL）进行离子交联, 被掺入制备 ε-PLL/CS-Arg/TCEP (ECAT) 复合纳米凝胶。结果表明，ECAT纳米凝胶对NTHi（）和（）的增殖表现出高效的抑制作用。此外，ECAT纳米凝胶可以有效抑制粘蛋白聚集体的形成，这表明纳米凝胶可能具有破坏呼吸道疾病中粘蛋白的潜力。此外，在卵清蛋白（OVA）/NTHi诱导的Balb/c小鼠中性粒细胞性哮喘模型中，通过塔雾化施用ECAT，有效降低了肺泡灌洗液中的中性粒细胞数量和血液中炎症细胞的百分比纳米凝胶，逆转气道高反应性（AHR）并减少中性粒细胞性哮喘小鼠的炎症。总之，构建ECAT纳米凝胶是一种可行的抗感染和抗炎治疗策略，在中性粒细胞性哮喘的临床治疗中表现出强大的潜力。