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

• Published in: Nature nanotechnology Vol. 17; no. 1; pp. 86 - 97
• Main Authors: Myerson, Jacob W., Patel, Priyal N., Rubey, Kathryn M., Zamora, Marco E., Zaleski, Michael H., Habibi, Nahal, Walsh, Landis R., Lee, Yi-Wei, Luther, David C., Ferguson, Laura T., Marcos-Contreras, Oscar A., Glassman, Patrick M., Mazaleuskaya, Liudmila L., Johnston, Ian, Hood, Elizabeth D., Shuvaeva, Tea, Wu, Jichuan, Zhang, Hong-Ying, Gregory, Jason V., Kiseleva, Raisa Y., Nong, Jia, Grosser, Tilo, Greineder, Colin F., Mitragotri, Samir, Worthen, George S., Rotello, Vincent M., Lahann, Joerg, Muzykantov, Vladimir R., Brenner, Jacob S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2022; Nature Publishing Group
• Subjects: 631/61/350/354; 639/166/985; 639/301/357/537; 639/925/352/152; 639/925/352/2734; Acute Disease; Agglutination - drug effects; Animals; Antibodies - pharmacology; Capillaries; Capsids; Chemistry and Materials Science; Cross-Linking Reagents - chemistry; Crosslinking; Dextrans - chemistry; Diapedesis; Edema; Electrostatic properties; Emergency response; Flow cytometry; Humans; Hydrophobicity; Immunohistochemistry; Inflammation; Inflammation - pathology; Leukocytes (neutrophilic); Lipopolysaccharides; Liposomes; Lung - diagnostic imaging; Lung - pathology; Lungs; Male; Materials Science; Mice; Mice, Inbred C57BL; Muramidase - metabolism; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Nanotechnology and Microengineering; Neutrophils; Neutrophils - drug effects; Neutrophils - pathology; Opsonin Proteins - metabolism; Opsonization; Proteins; Proteins - chemistry; Respiratory distress syndrome; Selectivity; Static Electricity; Therapeutic applications; Tissue Distribution - drug effects; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropism
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/s41565-021-00997-y

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. Neutrophils are the first responders in acute inflammatory events such as acute respiratory distress syndrome and tend to home to lung capillaries during acute inflammation, where they can cause tissue damage by diapedesis and secretion of specific molecules. Here the authors show that nanoparticles coated with agglutinated proteins selectively target activated neutrophils in inflamed lungs and can be used for imaging and therapeutic purposes.