Surface-Engineered Nanoliposomes by Chelating Ligands for Modulating the Neurotoxicity Associated with β-Amyloid Aggregates of Alzheimer’s disease

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.