Ligand-receptor interaction in the specific targeting of biomimetic peptide nanoparticles to lysophosphatidylcholine

Abstract

As nanotechnology is applied clinical medicine, nanoparticle-based therapy is emerging as a novel approach for the treatment of atherosclerosis. Ligand-receptor interaction affects the effectiveness of nanoparticle targeting therapy. In this study, the biomimetic peptide (BP-KFFVLK-WYKDGD) ligand specifically targeting the lysophosphatidylcholine (LPC) receptor in atherosclerotic plaques was constructed. The corresponding ligand-receptor interaction under different pH values was investigated by molecular dynamics simulation and experimental measurements. Results show that the interaction force between the peptide and LPC is greater than that of the peptide and human umbilical vein endothelial cell, clearly demonstrating the specific targeting of the peptide ligand to the LPC receptor. The ligand-receptor binding of peptide and LPC dominantly depends on Coulomb and van der Waals interactions. The YKDG amino acids of the peptide are the main fragment that binds to LPC. Compared with neutral environment at pH 7.4, the interaction forces between the peptide and oxidized low-density lipoprotein (oxLDL) decreased by 18.22 % and 45.87 % under acidic environments at pH 6.5 and 5.5, respectively, because of the change in oxLDL secondary structure and the release of LPC from oxLDL. Nevertheless, the peptide still has a strong binding capacity with oxLDL for the treatment of atherosclerosis.

Keywords: Atherosclerosis treatment; Biomimetic peptide ligand and lysophosphatidylcholine receptor; Molecular dynamics simulation and experimental measurements.