Applications of Prussian blue nanoparticles in the treatment of neurodegenerative diseases

Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are characterized by progressive neuronal dysfunction associated with oxidative stress, chronic neuroinflammation, mitochondrial impairment, and pathological protein aggregation. Despite advances in symptomatic treatments, effective disease-modifying therapies remain limited. This review examines the emerging role of Prussian blue nanoparticles (PBNPs) as multifunctional nanoplatforms for neurodegenerative diseases and related neurological conditions, including ischemic stroke and nerve regeneration. Their intrinsic enzyme-mimetic (nanozyme) activities enable the catalytic scavenging of reactive oxygen and nitrogen species, mimicking key antioxidant enzymes such as superoxide dismutase and catalase. PBNPs may also modulate neuroinflammation, microglial activation, and the aggregation of neurotoxic proteins, including β-amyloid and α-synuclein. Advances in nanoparticle engineering to improve brain delivery, targeting, and pharmacokinetics are highlighted. Finally, the review critically addresses toxicological challenges, including biodistribution, organ accumulation, degradation, long-term persistence, and the potential effects of surface modifications, which remain key considerations for the safe clinical translation of PBNP-based therapeutic and theranostic strategies.