Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment

Jacob W. Myerson; Priyal N. Patel; Nahal Habibi; Landis R. Walsh; Yi-Wei Lee; David C. Luther; Laura T. Ferguson; Michael H. Zaleski; Marco E. Zamora; Oscar A. Marcos-Contreras; Patrick M. Glassman; Ian Johnston; Elizabeth D. Hood; Tea Shuvaeva; Jason V. Gregory; Raisa Y. Kiseleva; Jia Nong; Kathryn M. Rubey; Colin F. Greineder; Samir Mitragotri; George S. Worthen; Vincent M. Rotello; Joerg Lahann; Vladimir R. Muzykantov; Jacob S. Brenner

Previous work has traced the neutrophil response to bacteria in the lungs, determining that pulmonary neutrophils pursue and engulf active bacteria following either intravenous infection or infection of the airspace in the lungs. 18, 34, 35 We injected heat-inactivated, oxidized, and fixed E. coli in naïve and IV-LPS-injured mice. With the bacteria stripped of their functional behavior, E. coli did not accumulate in the lungs of naïve control mice (1.47% of initial dose in the lungs, blue bars in Figure 1F ). However, pre-treatment with LPS to recapitulate the inflammatory response to infection led to enhanced accumulation of the deactivated E. coli in the lungs (7.69% of initial dose in the lungs, red bars in Figure 1F ). With E. coli structure maintained but E. coli function removed, the inactivated bacteria were taken up more avidly in lungs primed by an inflammatory injury.