Gold nanoparticles (AuNPs) cross the BBB and induce cytotoxicity in SH-SY5Y cells

Drugs delivery into the brain across the blood brain barrier (BBB) has always remained a challenging task. The central nervous system (CNS) is mainly protected by the blood brain barrier, which acts as a firewall to defend the brain from toxins, bacteria and viruses. The BBB allows for passive diffusion of small lipid-soluble molecules, whereas hydrophilic substances or molecules with high molecular weight have minimal passive permeation. Nanoparticles have generated a great deal of interest for their potential use in therapeutics drug delivery by passing the blood brain barrier (BBB). We explored the neuronal uptake of AuNPs both in vitro using SH-SY5Y human neuroblastoma cells and in vivo using direct brain injection in mice. In particular we used gold nanoparticles MMI-AuNPs stabilized with 2-mercapto-1-methylimidazole. For the in vitro studies, we incubated SH-SY5Y cells with 1x105 AuNPs for 20min, 1, 2 and 4 hrs. AuNP internalization was observed using a Leica microscope workstation B6000 equipped with an in vivo timelapse analysis capability. We confirmed our results using transmission electron microscopy (TEM). Our in vitro data demonstrated that gold-particles passed the cell membrane, clustered in the cytoplasm and induced apoptosis after 4 hrs of treatment. We confirmed our results using transmission electron microscopy (TEM). For in vivo, studies we injected a physiological solution containing 1x106 MMM-AuNPs into the carotid arteries of anesthetized mice. Fluorescence was evenly distributed in the neuronal cells but was not observed in glial cells, as demonstrated by GFAP and NeuN immunoistochemistry. Our data suggest that AuNPs cross the BBB and have useful imaging properties that rely on clustering in cells, which changes their emission spectrum from green to red. Specific properties of these nanoparticles may offer new advantages as potential pharmaco delivery tools in treatment of neurological diseases.