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

. 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.15.037564 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the .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 uptake of 75nm lysozyme-dextran nanogels (n=4 IV-LPS, n=4 naïve) and 200nm lysozyme-dextran nanogels (n=5 IV-LPS, n=5 naïve) in LPS-injured lungs, but not naïve lungs. Data for 130nm lysozyme-dextran nanogels is identical to that presented in Figure 2a. (b) Biodistributions of variant crosslinked albumin nanoparticles indicating uptake of albumin nanorods (n=3 IV-LPS, n=3 naïve) and bovine albumin nanoparticles (n=3 IV-LPS, n=3 naïve) in LPS-injured, but not naïve lungs. Data for human albumin nanoparticles is identical to that presented in Figure 2b . (c) Biodistributions of chargeagglutinated protein nanoparticles, indicating uptake of particles comprised of glutamate-tagged green fluorescent protein (E-GFP) and guanidine-tagged poly(oxanorborneneimide) (PONI) or particles comprised of E-GFP and guanidinetagged gold nanoparticles (Au) in LPS-injured (PONI: n=5, Au: n=3), but not naïve (PONI: n=4, Au: n=3) lungs. PONI/E-GFP data reflects tracing of both 131 I-labeled PONI and 125 I-labeled E-GFP. (d-e) Nanoparticles based on highly symmetric supramolecular organization of protein or nanoparticles not based on protein do not have tropism for inflamed lungs. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.15.037564 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the .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