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

Nanoparticle or protein biodistributions were tested by injecting radiolabeled nanoparticles or protein (suspended to 100 µL in PBS or 0.9% saline at a dose of 2.5 mg/kg with tracer quantities of radiolabeled material) in C57BL/6 male mice from Jackson Laboratories. Biodistributions in naïve mice were compared to biodistributions in several injury models. Biodistribution data were collected at 30 minutes after nanoparticle or protein injection, unless otherwise stated, as in pharmacokinetics studies. Briefly, blood was collected by vena cava draw and mice were sacrificed via terminal exsanguination and cervical dislocation. Organs were harvested and rinsed in . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 saline, and blood and organs were examined for nanoparticle or protein retention in a gamma counter (Perkin-Elmer). Nanoparticle or protein retention in harvested organs was compared to measured radioactivity in injected doses. For calculations of nanoparticle or protein concentration in organs, quantity of retained radioactivity was normalized to organ weights.