About: Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment
Creator	Hood, Elizabeth Brenner, Jacob Ferguson, Laura Glassman, Patrick Kiseleva, Raisa Mitragotri, Samir Muzykantov, Vladimir Myerson, Jacob Gregory, Jason Greineder, Colin Habibi, Nahal Johnston, Ian Lahann, Joerg Lee, Yi-Wei Luther, David Marcos-Contreras, Oscar Nong, Jia Patel, Priyal Rotello, Vincent Rubey, Kathryn Shuvaeva, Tea Walsh, Landis Worthen, George Zaleski, Michael Zamora, Marco
source	BioRxiv
abstract	Acute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries (“margination”). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections.
has issue date	2020-04-18(xsd:dateTime)
bibo:doi	10.1101/2020.04.15.037564
has license	biorxiv
sha1sum (hex)	cc89e35678f856eb6512f872785f1a0baf8ab901
schema:url	https://doi.org/10.1101/2020.04.15.037564
resource representing a document's title	Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment
schema:publication	bioRxiv
resource representing a document's body	covid:cc89e35678f856eb6512f872785f1a0baf8ab901#body_text
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