Near-Infrared Light-Activated Polydopamine Nanoparticles Conjugated With Transferrin Peptides for Enhanced Brain Accumulation.

The global rise in neurodegenerative diseases underscores the urgent need for effective drug delivery systems capable of crossing the blood-brain barrier (BBB). Here, we demonstrate that biodegradable polydopamine nanoparticles (PDA NPs) conjugated with transferrin peptides (Tf-PDA NPs), when activated by near-infrared (NIR) laser irradiation, can increase BBB permeability to Tf-PDA NPs both in vitro and in vivo. In vitro, NIR-activated Tf-PDA NPs significantly increased the permeability of brain endothelial cell monolayers compared to bare PDA NPs, without inducing cytotoxicity, compromising monolayer integrity, or triggering macrophage activation. In vivo, intravenous administration of Tf-PDA NPs followed by transcranial NIR laser stimulation resulted in enhanced BBB permeability, as evidenced by increased accumulation of Tf-PDA NPs and Evans Blue dye in the mouse brain parenchyma compared to control groups receiving bare PDA NPs. Collectively, these findings indicate that Tf-PDA NPs represent a promising light-responsive nanocarrier for targeted brain drug delivery. The synergistic combination of Tf peptide conjugation and the photothermal properties of PDA NPs enables efficient brain accumulation without eliciting inflammation, highlighting their potential for the treatment of a broad range of neurological disorders.