Polydopamine nanoparticles restore cognition via targeted dopamine delivery and septo-hippocampal cholinergic activation.

ABSTRACT: Altered dopamine (DA) neurotransmission in key brain circuits underlies cognitive deficits across psychiatric and neurological disorders by disrupting working memory, attention, and executive function. Here, we introduce a novel, carrier-free nanotherapeutic approach using polydopamine nanoparticles (PDA NPs)-synthesized via oxidative self-polymerization of DA hydrochloride-for targeted DA supplementation and cognitive rescue. Uniform, spherical PDA NPs (~250 nm) exhibit excellent biocompatibility and cross the blood-brain barrier via endocytosis. In acidic environments, they degrade to release DA, which is internalized by endothelial and neuronal cells and subsequently converted into downstream catecholamines. In a mouse model of lipopolysaccharide-induced cognitive impairment, PDA NP tre

SUBMITTER: Liu PM 

PROVIDER: S-EPMC12846747 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature