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

Naïve and IV LPS-injured mice were dosed with LDNGs labeled with 111 In via chelate conjugation to lysozyme. 111 In uptake in naïve and LPS-injured lungs was visualized with ex vivo SPECT-CT imaging to indicate capacity of LDNGs for imagingbased diagnosis of inflammatory lung injury ( Figure 5D ). 111 In signa was colocalized with anatomical CT images for reconstructions in Figure 5D . 111 In SPECT signal was detectable in LPS-injured lungs, but 111 In SPECT signal was at background level in naïve lungs (Supplementary Movies 4 and 5). Reduced SPECT signal in the liver of LPS-injured mice, in agreement with biodistribution data, was also evident in coregistration of SPECT imaging with full body skeletal CT imaging (Supplementary Movies 6 and 7). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.15.037564 doi: bioRxiv preprint Therefore, NAPs with tropism for marginated neutrophils have the ability to detect and assess ARDS-like inflammation via SPECT-CT imaging. Since those same NAPs do not accumulate in lungs afflicted with CPE, NAPs have potential for differential diagnosis of acute lung inflammation against CPE.