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

LDNG biodistributions were also assessed in mice undergoing alternative forms of LPS-induced inflammation. Intratracheal (IT) instillation of LPS led to concentration of LDNGs in the lungs at 81.31 %ID/g. Liver and spleen LDNG uptake was also reduced following IT LPS injury, leading to a 45-fold increase in the lungs:liver LDNG localization ratio induced by IT LPS injury (Supplementary Figure 5) . As with IV LPS injury, IT LPS administration leads to neutrophil-mediated vascular injury focused in the lungs. 14 Mice were administered LPS via footpad injection to provide a model of systemic inflammation originating in lymphatic drainage. 39 LDNG uptake in the lungs and in the legs was enhanced by footpad LPS administration. At 6 hours after footpad LPS administration, LDNGs concentrated in the lungs at 59.29 %ID/g, an 11-fold increase over naïve. At 24 hours, LDNGs concentrated in the lungs at 202.64 %ID/g (Supplementary Figure 6A) . Total LDNG accumulation in the legs accounted for 0.85% of initial dose (%ID) in naïve mice, 2.65 %ID in mice 6 hours after footpad LPS injection, and 8.34 %ID at 24 hours after footpad injection (Supplementary Figure 6B) , indicating LDNGs can concentrate in inflamed vasculature outside the lungs.