Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation
| Autor: | Vincent M. Rotello, Laura T. Ferguson, Tea Shuvaeva, Nahal Habibi, Colin F. Greineder, David C. Luther, George S Worthen, Priyal Patel, Landis R. Walsh, Jacob W. Myerson, Oscar A. Marcos-Contreras, Jia Nong, Jichuan Wu, Hong-Ying Zhang, Liudmila L. Mazaleuskaya, Marco E Zamora, Joerg Lahann, Ian Johnston, Michael H Zaleski, Jason V. Gregory, Vladimir R. Muzykantov, Raisa Yu Kiseleva, Elizabeth D. Hood, Kathryn M Rubey, Samir Mitragotri, Jacob S. Brenner, Tilo Grosser, Yi-Wei Lee, Patrick M. Glassman |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Lipopolysaccharides
Male Agglutination Neutrophils Static Electricity Biomedical Engineering Bioengineering Inflammation Antibodies Flow cytometry mental disorders medicine Animals Humans Tissue Distribution General Materials Science Electrical and Electronic Engineering Lung Tropism Tomography Emission-Computed Single-Photon Liposome medicine.diagnostic_test Chemistry fungi Proteins Dextrans Opsonin Proteins respiratory system Condensed Matter Physics Atomic and Molecular Physics and Optics respiratory tract diseases Cell biology Mice Inbred C57BL Nap Antibody opsonization Cross-Linking Reagents medicine.anatomical_structure Acute Disease Liposomes Nanoparticles Muramidase medicine.symptom Tomography X-Ray Computed psychological phenomena and processes Homing (hematopoietic) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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