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

We then demonstrate proof of concept for NAPs as diagnostic and therapeutic tools for ARDS. We show; a) 111 In-labeled NAPs provide diagnostic imaging contrast that distinguishes inflammatory lung injury from cardiogenic pulmonary edema; b) NAPliposomes can significantly ameliorate edema in a mouse model of severe ARDS; c) NAPs, but not crystalline protein nanostructures, accumulate in ex vivo human lungs rejected for transplant due to ARDS-like conditions. Collectively, our results will demonstrate that supramolecular organization of protein, namely protein agglutination, predicts strong, intrinsic nanoparticle tropism for marginated neutrophils. This finding indicates that NAPs, encompassing a wide range of nanoparticles based on or incorporating protein, have biodistributions that are responsive to inflammation. NAPs could be useful beyond ARDS, since marginated neutrophils play a pathogenic role in a diverse array of inflammatory diseases, including infections, heart attack, and stroke. [10] [11] [12] [13] [14] But our findings provide a clear path forward for using NAPs to improve diagnosis and treatment of ARDS.