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 i...Continue Reading
References
Inorganic mercury detection and controlled release of chelating agents from ion-responsive liposomes
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