Wang Xu, Zhou Hao, Li Dan, Zhao Zhe, Peng Ke, Xu Xiang, Wang Jia-Jia, Wang Yang, Wang Jun, Zhang Jing-Jing, Wan Shuang-Shuang, Shi Mai-Qing, Chen Jun, Ding Xian-Guang, Ji Fu-Hai
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu , China.
Biomater Res. 2025 Apr 2;29:0172. doi: 10.34133/bmr.0172. eCollection 2025.
Although extensive antibiotic regimens have been implemented to address pathogen-infected pneumonia, existing strategies are constrained in their efficacy against intracellular bacteria, a prominent contributor to antibiotic resistance. In addition, the concurrent occurrence of a cytokine storm during antibiotic therapy presents a formidable obstacle in the management of pneumonia caused by pathogens. In the present study, an infection-targeting system that leverages M2-macrophage-derived vesicles [exosomes (Exos)] as vehicles to convey antibiotics (antibiotics@Exos) was developed for effective pneumonia management. The proposed system can enable antibiotics to be specifically delivered to infected macrophages in pneumonia through homotypic recognition and was found to exhibit an exceptional intracellular bactericidal effect. Moreover, M2-type vesicles exhibit a high degree of efficiency in reprogramming inflammatory macrophages toward an anti-inflammatory phenotype. As a result, the administration of antibiotics@Exos was found to substantical decrease the level of the infiltrated inflammatory cells and alleviate the inflammatory factor storm in the lungs of acute lung injury mice. This intervention resulted in the alleviation of reactive-oxygen-species-induced damage, reduction of pulmonary edema, and successful pneumonia treatment. This bioactive vesicle delivery system effectively compensates for the limitations of traditional antibiotic therapy regimens with pluralism effects, paving a new strategy for serious infectious diseases, especially acute pneumonia treatment.
尽管已实施广泛的抗生素方案来应对病原体感染的肺炎，但现有策略在对抗细胞内细菌方面的疗效受到限制，而细胞内细菌是抗生素耐药性的一个主要促成因素。此外，抗生素治疗期间细胞因子风暴的同时出现给病原体引起的肺炎的治疗带来了巨大障碍。在本研究中，开发了一种以感染为靶点的系统，该系统利用M2巨噬细胞衍生的囊泡[外泌体（Exos）]作为载体来输送抗生素（抗生素@Exos），以有效治疗肺炎。所提出的系统能够通过同源识别使抗生素特异性地递送至肺炎中受感染的巨噬细胞，并被发现具有卓越的细胞内杀菌效果。此外，M2型囊泡在将炎性巨噬细胞重编程为抗炎表型方面表现出高度的效率。结果，发现给予抗生素@Exos可显著降低急性肺损伤小鼠肺部浸润炎性细胞的水平，并减轻炎性因子风暴。这种干预减轻了活性氧诱导的损伤，减轻了肺水肿，并成功治疗了肺炎。这种生物活性囊泡递送系统有效地弥补了传统抗生素治疗方案的局限性，具有多种作用，为严重传染病，尤其是急性肺炎的治疗开辟了新策略。
