Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study

Abstract

Blood brain barrier (BBB) is a dynamic interface, comprising polarized endothelial cells, that separates the brain from the circulatory system. The highly protective nature of this tight junction impairs diagnosis and treatment of brain disorders. In this study, we designed a sub atomic size, near infrared emitting, dual function glutathione gold cluster with high fluorescence yield to facilitate permeability of BBB, for imaging applications and drug delivery. The gold cluster was then modified with Levodopa (L-dopa), to utilize the large amino acid transporter 1 (LAT1) pathways to enhance brain entry. Uptake and permeability of the nanoprobes were demonstrated using an established model of BBB, comprising brain endothelial cells (bEnd.3). The uptake and the clearance of L-dopa modified cluster was faster than the glutathione cluster. L-Dopa modified cluster supports the slow and sustained delivery of a model drug, pilocarpine, to the brain. Results of in vivo imaging and drug release in normal mice hold promise for considering the probe for early diagnosis of brain diseases, when the barrier is not disrupted, and for subsequent drug treatment.