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

In conclusion, supramolecular organization in nanoparticle structure predicts nanoparticle uptake in pulmonary marginated neutrophils during acute inflammation. Specifically, nanoparticles with agglutinated protein (NAPs) accumulate in marginated neutrophils, while nanoparticles with more symmetric protein organization do not. NAP tropism for neutrophils allowed us to develop NAPs as diagnostics and therapeutics for ARDS, and even to demonstrate NAP uptake in inflamed human lungs. Future work may more deeply explore therapeutic effects of NAPs in ARDS and other diseases in which neutrophils play key roles. This study also obviates future testing of supramolecular organization as a variable in in vivo behavior of nanoparticles, including screens of tropism for other pathologies and cell types. These studies could in turn guide engineering of new particles with intrinsic cell tropisms, as with our engineering of NAP-liposomes with neutrophil tropism. These "targeting" behaviors, requiring no affinity moieties, may apply to a wide variety of nanomaterials. But our current findings with neutrophil-tropic NAPs indicate that many protein-based and protein-coated nanoparticles could be untapped resources for treatment and diagnosis of devastating inflammatory disorders like ARDS.