A Fibrinogen-Derived Peptide Provides Intercellular Adhesion Molecule-1-Specific Targeting and Intraendothelial Transport of Polymer Nanocarriers in Human Cell Cultures and Mice

• DOI: 10.1124/jpet.111.185579
• Publication Date: 2011-12-08T06:03:58Z
• Authors: Carmen Garnacho; Daniel Serrano; Silvia Muro
• Keywords: Nanocarriers

Intercellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein expressed on activated endothelium and many other cells, represents suitable target for delivery of drug nanocarriers (NCs) to disease areas. Numerous works have shown efficient targeting intracellular transport ICAM-1-targeted NCs, rendering significant therapeutic potential. This is the case enzyme treatment multitissue lysosomal storage disorders. However, those studies used formulations targeted ICAM-1 by antibodies (anti-ICAM NCs). poses an obstacle preclinical evaluation long-term such chronic maladies, caused immunogenicity foreign proteins administered animals, compelling development alternative strategies. In this work, we radioisotope tracing, fluorescence electron microscopy, in vitro, cell cultures, mouse models evaluate polymer 17-mer linear peptide derived from ICAM-1-binding sequence fibrinogen (γ3). Our results show that γ3 NCs with efficiency specificity similar anti-ICAM determined using immobilized ICAM-1, native endothelial intravenous administration mice. Furthermore, are internalized cells culture vivo transported lysosomes via molecule-mediated endocytosis, without apparent disruption junctions, counterparts. The degree conservation its cognate site among species (e.g., mouse, chimpanzee, humans) reflects interspecies found providing avenue exploring translation ICAM-1-targeting platforms and, perhaps, future clinical realm.