No abstract

This study shows that supramolecular arrangement of proteins in nanoparticle structure predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of n anoparticles with a gglutinated p rotein (NAPs), defined by arrangement of protein in or on the nanoparticles via; a) hydrophobic interactions; b) crosslinking; c) electrostatic interactions. Nanoparticles with symmetric protein arrangement ( e.g. , 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; a) demonstrate diagnostic imaging of ALI with NAPs; b) show NAP tropism for inflamed human donor lungs; c) show NAPs can remediate pulmonary edema in ALI. This work demonstrates structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI.

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.