Human breath contains many volatile metabolites. However, few breath tests are currently used in the clinic to monitor disease due to bottlenecks in biomarker identification. Here we engineered breath biomarkers for respiratory disease by local delivery of protease-sensing nanoparticles to the lungs. The nanosensors shed volatile reporters upon cleavage by neutrophil elastase, an inflammation-associated protease with elevated activity in lung diseases such as bacterial infection and alpha-1 antitrypsin deficiency. After intrapulmonary delivery into mouse models with acute lung inflammation, the volatile reporters are released and expelled in breath at levels detectable by mass spectrometry. These breath signals can identify diseased mice with high sensitivity as early as 10 min after nanosensor administration. Using these nanosensors, we performed serial breath tests to monitor dynamic changes in neutrophil elastase activity during lung infection and to assess the efficacy of a protease inhibitor therapy targeting neutrophil elastase for the treatment of alpha-1 antitrypsin deficiency.

人类的呼吸含有许多挥发性代谢物。然而，由于生物标志物识别的瓶颈，目前临床上很少使用呼气测试来监测疾病。在这里，我们通过将蛋白酶感应纳米粒子局部递送到肺部来设计呼吸系统疾病的呼吸生物标志物。纳米传感器在被中性粒细胞弹性蛋白酶裂解后释放出挥发性报告分子，中性粒细胞弹性蛋白酶是一种与炎症相关的蛋白酶，在细菌感染和 α-1 抗胰蛋白酶缺乏等肺部疾病中具有较高的活性。肺内递送至患有急性肺部炎症的小鼠模型后，挥发性报道分子以质谱可检测的水平释放并通过呼吸排出。这些呼吸信号最早可以在纳米传感器给药后 10 分钟内以高灵敏度识别患病小鼠。使用这些纳米传感器，我们进行了一系列呼吸测试，以监测肺部感染期间中性粒细胞弹性蛋白酶活性的动态变化，并评估针对中性粒细胞弹性蛋白酶的蛋白酶抑制剂治疗α-1抗胰蛋白酶缺乏症的疗效。