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Novel Nanoparticle Composition Targeting Marginated Leukocytes
University of Pennsylvania
Nanoparticle
Inflammatory disease
Hit To Lead or Lead Optimization
• Arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions.
• Acute inflammatory diseases, including sepsis, pneumonia, and acute respiratory distress syndrome (ARDS), account for over 1.5 million hospitalizations and 300,000 deaths per year in the US. These diseases all share a common cellular player known as marginated leukocytes.
• Marginated leukocytes are white blood cells that accumulate in the blood vessels of inflamed organs and potentiate disease progression by releasing toxins and pro-inflammatory cytokines and induce clotting and further inflammation. Accumulation of marginated leukocytes can ultimately lead to organ dysfunction.
• Inventors developed a molecular label consisting of an IgG antibody bound to dibenzocyclooctyne (D20 tag). When attached to nanoparticles, the D20 tag almost exclusively localized to marginated leukocytes to alleviate disease symptoms in a small animal model of acute inflammatory injury.
• Using the D20 tag to target marginated leukocytes with imaging agents or drugs could better enable clinical diagnosis and treatment of acute inflammatory diseases.
WO2021/113519A1
Supramolecular Arrangement of Protein in Nanoparticle Structures Predicts Nanoparticle Tropism for Neutrophils in Acute Lung
Inflammation. Nat Nanotechnol. (2022)
