急性呼吸窘迫综合征
促炎细胞因子
炎症
医学
胞外囊泡
肺
CXCL1型
免疫学
微泡
内科学
生物
趋化因子
生物化学
基因
小RNA
作者
Ana I Salazar-Puerta,María A. Rincon-Benavides,Tatiana Z. Cuellar‐Gaviria,Julian Aldana,Gabriela Vasquez Martinez,Lilibeth Ortega‐Pineda,Devleena Das,Daniel Dodd,Charles A Spencer,Binbin Deng,David W. McComb,Joshua A. Englert,Samir N. Ghadiali,Diana Zepeda‐Orozco,Loren E. Wold,Daniel Gallego‐Perez,Natalia Higuita‐Castro
标识
DOI:10.1002/adma.202210579
摘要
Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in the USA. ARDS patients suffer from severe refractory hypoxemia, alveolar-capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead to intensive care unit admission, prolonged hospitalization, and increased disability-adjusted life years. Currently, there is no cure or FDA-approved therapy for ARDS. This work describes the implementation of engineered extracellular vesicle (eEV)-based nanocarriers for targeted nonviral delivery of anti-inflammatory payloads to the inflamed/injured lung. The results show the ability of surfactant protein A (SPA)-functionalized IL-4- and IL-10-loaded eEVs to promote intrapulmonary retention and reduce inflammation, both in vitro and in vivo. Significant attenuation is observed in tissue damage, proinflammatory cytokine secretion, macrophage activation, influx of protein-rich fluid, and neutrophil infiltration into the alveolar space as early as 6 h post-eEVs treatment. Additionally, metabolomics analyses show that eEV treatment causes significant changes in the metabolic profile of inflamed lungs, driving the secretion of key anti-inflammatory metabolites. Altogether, these results establish the potential of eEVs derived from dermal fibroblasts to reduce inflammation, tissue damage, and the prevalence/progression of injury during ARDS via nonviral delivery of anti-inflammatory genes/transcripts.
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