Intranasal Delivery of Gallium-Quercetin Nanoparticles for Multi-Target Ferroptosis Inhibition in Parkinson's Disease.

Ferroptosis contributes to Parkinson's disease (PD) through interconnected processes including iron dysregulation, oxidative stress, and mitochondrial dysfunction, yet current therapies targeting single pathways remain insufficient. Herein, we developed gallium-quercetin nanoparticles (GQNPs) as an intranasally deliverable nanoplatform for multi-target ferroptosis inhibition. In vitro, GQNPs suppressed ferroptosis by coordinating iron regulation and antioxidation. Ga3 + interfered with transferrin-mediated iron uptake to restrict iron influx, while quercetin reduced oxidative stress and supported iron homeostasis, thereby decreasing ROS accumulation and improving mitochondrial function. In vivo, intranasal delivery of GQNPs effectively bypassed the blood-brain barrier to recover motor coordination and cognitive function in PD mice. By integrating iron regulation, antioxidant activity, and mitochondrial protection within a single nanoplatform, this work highlights gallium-based coordination nanoparticles as a promising therapeutic strategy for ferroptosis-associated neurodegenerative diseases.