L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles

The blood–brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB to deliver therapies into the brain. The drug L-DOPA efficiently and specifically crosses the BBB via the large neutral amino acid transporter (LAT)-1 protein to enter the brain. Thus, we synthesized L-DOPA-functionalized multi-branched nanoflower-like gold nanoparticles (L-DOPA-AuNFs) using a seed-mediated method involving catechols as a direct reducing-cum-capping agent, and examined their ability to cross the BBB to act as brain-penetrating nanovehicles. We show that L-DOPA-AuNFs efficiently penetrate the BBB compared to similarly sized and shaped AuNFs functionalized with a non-targeting ligand. Furthermore, we show that L-DOPA-AuNFs are efficiently internalized by brain macrophages without inducing inflammation. These results demonstrate the application of L-DOPA-AuNFs as a non-inflammatory BBB-penetrating nanovehicle to efficiently deliver therapies into the brain. There is an urgent need to develop vehicles capable of penetrating the blood–brain barrier (BBB) for specific brain delivery of therapies against disorders such as Parkinson's disease. We have developed multi-branched gold nanoparticles (AuNPs) functionalized with the BBB-targeting ligand L-DOPA and demonstrate their efficient and ligand-dependent transportation across the BBB. Furthermore, we demonstrate efficient uptake of L-DOPA-AuNPs by brain macrophages without induction of inflammation. These results lay the foundations for developing L-DOPA-functionalized AuNPs as an efficient and safe platform for the delivery of therapies into the brain. [Display omitted]