Preparation of functional liposomes with peptide ligands and their binding to cell membranes.
ABSTRACT Two novel lipopeptides, which have the peptide ligands [alpha-melanocyte stimulating hormone (alpha-MSH)] sequence and repeated [Gly-Arg-Gly-Asp-Se (GRGDS) sequence], are designed, synthesized by the solid-phase method, and introduced into liposome membranes by the freeze-thaw method. These liposomes bearing the peptide ligands on their surface are expected to bind to cell membranes. We have confirmed that the lipopeptides are introduced into liposome membranes almost quantitatively, while such a high degree of incorporation has not been accomplished in conventional methods. In this respect, the present method is superior to prepare surface-modified liposomes that are applicable to drug carriers and so on. We have also confirmed by using immunoelectron microscopy that the peptide ligands are actually located in an aqueous phase. It has been shown by flow cytometry that the liposome bearing alpha-MSH peptide ligand binds to B16 cells and the liposome bearing the repeated GRGDS sequence binds to NIH3T3 cells.
Article: Surface-Engineered Nanoliposomes by Chelating Ligands for Modulating the Neurotoxicity Associated with β-Amyloid Aggregates of Alzheimer's disease.[show abstract] [hide abstract]
ABSTRACT: To develop chelating ligand-bound nanoliposomes (NLPs) for the prevention and reversal of β-Amyloid (Aβ) aggregation associated with promoting neurotoxicity in Alzheimer disease (AD). Four different chelating ligands (CuAc, EDTA, histidine and ZnAc) were surface-engineered onto NLPs using either covalent or non-covalent conjugation. Successful conjugation of chelating ligands onto the surface of NLPs was confirmed by characterization studies: SEM, TEM and FTIR analysis. Chelation energetics of EDTA with Cu(II)/Zn(II)-Aβ(10-21) and nanoformation of emulsified polymers were computed and corroborated with experimental and analytical data using chemometric molecular modeling. The modified NLPs produced were spherical in shape, 127-178 nm in size, with polydispersity index from 0.217-0.920 and zeta potential range of -9.59 to -37.3 mV. Conjugation efficiencies were 30-76 %, which confirmed that chelating ligands were attached to the NLP surface. In vitro and ex vivo results elucidated the effectiveness of chelating ligand-bound NLPs for prevention of CuAβ(1-42) or ZnAβ(1-42) aggregate buildup associated with neurotoxicity in PC12 neuronal cells, as well as promotion of intracellular uptake in the presence of Cu(II) or Zn(II) metal ions.Pharmaceutical Research 05/2012; 29(11):3075-89. · 4.09 Impact Factor