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

Liposomes and polystyrene NPs were studied as example NPs that are not structurally based on proteins. DOTA chelate-containing lipids were incorporated into bare liposomes, allowing labeling with 111 In tracer for biodistribution studies. Carboxylate polystyrene NPs were coupled to trace amounts of 125 I-labeled IgG via EDCI-mediated carboxy-amine coupling. Liposomes had a diameter of 103.6±8.7 nm (PDI 0.09±0.01) and IgG-polystyrene NPs had a diameter of 230.5±2.8 nm (PDI 0.14±0.01) (Supplementary Figure 1C -D). Liposomes accumulated in inflamed lungs at a concentration of 16.89 %ID/g, accounting for no significant change against naïve lungs. LPS injury actually induced a reduction in the lungs:liver metric, from 0.20 for naïve mice to 0.15 for LPS-injured mice. Polystyrene NPs accumulated in inflamed lungs at 11.67 %ID/g (1.75% initial dose), so IV LPS injury did in fact induce increased levels of NP uptake in the lungs, from a concentration of 2.40 %ID/g in the naïve lungs ( Figure 3E, Supplementary Figure 12 ). However, neither bare liposomes nor polystyrene NPs were drawn to LPS-injured lungs in significant concentrations.