Engineering synthetic breath biomarkers for respiratory disease.
Engineering synthetic breath biomarkers for respiratory disease.
复制标题
DOI：
10.1038/s41565-020-0723-4
复制
发表时间：
2020-09
影响因子：
38.3
通讯作者：
Bhatia SN
中科院分区：
文献类型：
--
作者：
Chan LW;Anahtar MN;Ong TH;Hern KE;Kunz RR;Bhatia SN
人体呼气中含有许多挥发性代谢物。然而，由于生物标志物识别的瓶颈，目前只有少数呼气测试在临床上用于监测疾病。在这里，我们展示了我们可以通过将具有蛋白酶反应的纳米颗粒局部输送到肺部来设计呼吸系统疾病的呼吸生物标记物。在这项工作中，我们建立和优化了纳米传感器，在中性粒细胞弹性蛋白酶切割时释放挥发性报告，中性粒细胞弹性蛋白酶是一种在包括细菌感染和α-1抗胰蛋白酶缺乏症(AATD)在内的多种肺部病理中具有高活性的蛋白酶。我们证明，在肺内注射到患有急性肺部炎症的小鼠模型中后，挥发性记者从纳米传感器中解放出来，并在呼吸中被排出，达到质谱学可以检测到的水平。此外，呼吸信号可以在给药10分钟后以高灵敏度识别患病的小鼠。使用我们的纳米传感器，我们能够完成一系列呼气测试，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，并评估直接针对中性粒细胞弹性酶治疗AATD的蛋白酶抑制剂疗法的疗效。
Human breath contains many volatile metabolites. However, only a handful of breath tests are currently used in the clinic to monitor disease due to bottlenecks in biomarker identification. Here we show that we can engineer breath biomarkers for respiratory disease by local delivery of protease-responsive nanoparticles to the lungs. In this work, we built and optimized nanosensors that shed volatile reporters upon cleavage by neutrophil elastase, a protease with elevated activity in multiple lung pathologies including bacterial infection and alpha-1 antitrypsin deficiency (AATD). We demonstrate that, after intrapulmonary delivery into mouse models with acute lung inflammation, volatile reporters are liberated from nanosensors and expelled in breath at levels detectable by mass spectrometry. Furthermore, breath signals can identify diseased mice with high sensitivity as early as 10 min after nanosensor administration. Using our nanosensors, we were able to complete serial breath tests to monitor dynamic changes in neutrophil elastase activity during lung infection and assess the efficacy of a protease inhibitor therapy that directly targets neutrophil elastase for treatment of AATD.
登录
查看更多内容
影响因子：
17.1
作者：
Kirkpatrick JD;Warren AD;Soleimany AP;Westcott PMK;Voog JC;Martin-Alonso C;Fleming HE;Tammela T;Jacks T;Bhatia SN
通讯作者：
Bhatia SN
影响因子：
3.8
作者：
Gursahani, Hema;Riggs-Sauthier, Jennifer;Fishburn, C. Simone
通讯作者：
Fishburn, C. Simone
影响因子：
3.8
作者：
Bishai, William R.;Timmins, Graham S.
通讯作者：
Timmins, Graham S.
影响因子：
11.1
作者：
Buss CG;Dudani JS;Akana RTK;Fleming HE;Bhatia SN
通讯作者：
Bhatia SN
影响因子：
38.3
作者：
Loynachan, Colleen N.;Soleimany, Ava P.;Stevens, Molly M.
通讯作者：
Stevens, Molly M.