Antibody-conjugated PEGylated cerium oxide nanoparticles for specific targeting of Aβ aggregates modulate neuronal survival pathways

Annamaria CIMINI, Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology Temple University

Oxidative stress has found to be associated with the progression of neurodegenerative diseases such  as Alzheimer’s, Parkinson’s, Lou Gehrig’s, etc. In the recent years, cerium oxide nanoparticles (CNPs) have been studied as potent antioxidant agents able to exert neuroprotective effects. This work reports the design of polyethylene glycol (PEG)-coated and anti-Aβ antibody-conjugated CNPs for the selective delivering of nanoceria to Aβ aggregates, and the protective effects against oxidative stress/Aβ-mediated neurodegeneration. In this study PEG-coated and anti Aβ antibody-conjugated antioxidant nanoparticles (Ab-CNPs-PEG) were developed, and their effects on neuronal survival and brain-derived neurotrophic factor (BDNF) signaling pathway were examined in an in vitro model of Alzheimer’s disease. By modulating the BDNF signaling pathway Ab-CNPs-PEG specifically targets the Aβ aggregates, and concomitant rescues neuronal survival. This proof of concept work may allow in the future, once validated in vivo, the selective delivery of CNPs only to affected brain areas.

 
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