Severe pneumonia caused by bacteria remains a serious clinical challenge, because the mucus in the lower respiratory tract hinders the effective utilization of antibiotics. Thus, drug delivery systems with mucus-penetrating and infection-responsive releasing capabilities show great significance for lung infection treatment. Herein, based on natural polysaccharide oxidized soluble starch (OSS), a responsive nano-agent (OTP) that could overcome mucus barrier was designed and fabricated for lung infection therapy. By Schiff base reaction and non-covalent interaction, OSS was crosslinked with tobramycin (TOB), and the dispersity and mucus-penetrating properties were enhanced by PEGylation. The loaded TOB could be responsively released by the triggering of slightly acidic environment of infection, owning to the pH-sensitive imine bond, which improved the drug delivery efficiency to the infected area. The OTP samples had efficient antibacterial property and good biocompatibility. Due to the hydrophilic property, small size and positively charged surface, OTP showed high performance to penetrate the mucus layer, and could eliminate bacteria inside biofilm. The in vivo efficacy of OTP was demonstrated by a pneumonia animal modal, which could inhibit lung infection within 3 d. This work provided a flexible and effective strategy for constructing drug delivery system to treat pneumonia by inhalation, which had broad prospects in the clinical treatment of severe lung infections.

由细菌引起的重症肺炎仍然是一个严峻的临床挑战，因为下呼吸道的粘液阻碍了抗生素的有效利用。因此，具有粘液穿透和感染响应释放能力的药物输送系统对肺部感染治疗具有重要意义。在此，基于天然多糖氧化可溶性淀粉（OSS），设计并制造了一种可以克服粘液屏障的响应性纳米剂（OTP），用于肺部感染治疗。通过席夫碱反应和非共价相互作用，OSS与妥布霉素（TOB）交联，聚乙二醇化增强了分散性和粘液穿透性。由于 pH 敏感的亚胺键，负载的 TOB 可以通过触发微酸性感染环境响应释放，从而提高了向感染区域的药物输送效率。OTP样品具有高效的抗菌性能和良好的生物相容性。由于亲水性、小尺寸和带正电荷的表面，OTP显示出高效的穿透粘液层，并能消除生物膜内的细菌。这肺炎动物模式证明了OTP的体内功效，该模式可在3 d内抑制肺部感染。该工作为构建吸入治疗肺炎的给药系统提供了灵活有效的策略，在重症肺部感染的临床治疗中具有广阔的前景。