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

Nat Nanotechnol. 2022 Jan;17(1):86-97. doi: 10.1038/s41565-021-00997-y. Epub 2021 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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


  • Antibodies
  • Cross-Linking Reagents
  • Dextrans
  • Lipopolysaccharides
  • Liposomes
  • Opsonin Proteins
  • Proteins
  • Muramidase