Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications

Abstract

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-β protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects

“…By detecting with Thioflavin T fluorescence the presence of amyloid aggregates (Aβ1-42), a high signal was observed in the presence of the iron chelators (DFO, GC-DFO, and NB-GC-DFO) in comparison with Fe 3+ , confirming that iron chelation can effectively prevent Aβ misfolding [114].…”

“…No sign of NBs toxicity was present neither in the MTT nor in the LDH test at proper dilution, and no induced DOPAn loss was detected [114].…”

“…The same research group synthesized GC-DFO conjugate nanobubbles (GC-DFO NBs), able to effectively chelate Fe 3+ , forming a complex able to retain or even enhance the chelating ability of DFO at low iron concentrations [114].…”