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Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation
Journal article   Open access   Peer reviewed

Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation

Jacob W Myerson, Priyal N Patel, Kathryn M Rubey, Marco E Zamora, Michael H Zaleski, Nahal Habibi, Landis R Walsh, Yi-Wei Lee, David C Luther, Laura T Ferguson, …
Nature nanotechnology, v 17(1), pp 86-97
Jan 2022
PMID: 34795440
url
https://www.nature.com/articles/s41565-021-00997-y.pdfView
Published, Version of Record (VoR)Open Access (License Unspecified) Open
url
https://doi.org/10.1038/s41565-021-00997-yView
Published, Version of Record (VoR) Open

Abstract

Acute Disease Agglutination - drug effects Animals Antibodies - pharmacology Cross-Linking Reagents - chemistry Dextrans - chemistry Humans Inflammation - pathology Lipopolysaccharides Liposomes Lung - diagnostic imaging Lung - pathology Male Mice, Inbred C57BL Muramidase - metabolism Nanoparticles - chemistry Neutrophils - drug effects Neutrophils - pathology Opsonin Proteins - metabolism Proteins - chemistry Static Electricity Tissue Distribution - drug effects Tomography, Emission-Computed, Single-Photon Tomography, X-Ray Computed
This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Materials Science, Multidisciplinary
Nanoscience & Nanotechnology
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