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

DBCO(20X)-IgG liposomes, LDNGs, and bare liposomes were compared for effects on vascular permeability in model ARDS. NPs were administered as an IV bolus (20 mg per kg body weight) two hours after nebulized LPS administration. As in untreated mice, BAL fluid was harvested and analyzed at 24 hours after exposure to nebulized LPS. Bare liposomes or LDNGs did not have significant effects on vascular injury induced by nebulized LPS, as measured by either leukocyte or protein concentration in BAL fluid ( Figure 6 , red and green bars). DBCO(20X)-IgG liposomes, however, had a significant salient effect on both protein leakage and cellular infiltration in the BAL ( Figure 6 , brown bars). With DBCO(20X)-IgG liposomes administered two hours after nebulized LPS, CD45-positive cells and neutrophils in BAL were reduced to concentrations of 3.04x10 5 and 3.48x10 5 cells per mL, respectively. Protein concentration in the BAL was reduced to 0.21 mg/mL by DBCO(20X)-IgG liposome treatment. As measured by protection against cellular or protein leakage, relative to untreated mice, DBCO(20X)-IgG liposomes provided 59.6% protection against leukocyte leakage, 49.7% protection against neutrophil leakage, and 67.4% protection against protein leakage. DBCO(20X)-IgG liposomes, without any drug, altered the course of inflammatory lung injury to limit protein and leukocyte edema in the alveoli.