Controlling ligand surface density optimizes nanoparticle binding to ICAM-1.

ABSTRACT: During infection, pathogens utilize surface receptors to gain entry into intracellular compartments. Multiple receptor-ligand interactions that lead to pathogen internalization have been identified and the importance of multivalent ligand binding as a means to facilitate internalization has emerged. The effect of ligand density, however, is less well known. In this study, ligand density was examined using poly(DL-lactic-co-glycolic acid) nanoparticles (PLGA NPs). A cyclic peptide, cLABL, was used as a targeting moiety, as it is a known ligand for intercellular cell adhesion molecule-1 (ICAM-1). To modulate the number of reactive sites on the surface of PLGA NPs, modified Pluronic with carboxyl groups and Pluronic with hydroxyl groups were combined in different ratios and the particle properties were examined. Utilizing a surfactant mixture directly affected the particle charge and the number of reactive sites for cLABL conjugation. The surface density of cLABL peptide increased as the relative amount of reactive Pluronic was increased. Studies using carcinomic human alveolar basal epithelial cells (A549) showed that cLABL density might be optimized to improve cellular uptake. These results complement other studies, suggesting that surface density of the targeting moiety on the NP surface should be considered to enhance the effect of ligands used for cell targeting.

SUBMITTER: Fakhari A 

PROVIDER: S-EPMC4245447 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature