Gold nanoparticles (AuNPs) have been extensively used as nanomaterials for theranostic applications due to their multifunctional characteristics in therapeutics, imaging, and surface modification. In this study, the unique functionalities of exosome-derived membranes were combined with synthetic AuNPs for targeted delivery to brain cells. Here, researchers from NANOTEC report the surface modification of AuNPs with brain-targeted exosomes derived from genetically engineered mammalian cells by using the mechanical method or extrusion to create these novel nanomaterials. The unique targeting properties of the AuNPs after fabrication with the brain-targeted exosomes was demonstrated by their binding to brain cells under laminar flow conditions as well as their enhanced transport across the blood brain barrier. In a further demonstration of their ability to target brain cells, in vivo bioluminescence imaging revealed that targeted-exosome coated AuNPs accumulated in the mouse brain after intravenous injection. The surface modification of synthetic AuNPs with the brain-targeted exosome demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified AuNPs to penetrate the brain.
Schematic representation of gold nanoparticle
surface functionalization through exosome coating
In this approach, exosome-producing cells were transiently transfected with a pcDNA GNSTM-3-RVG-10-Lamp2b-HA vector to express Lamp2b fusion protein fused in frame with the neuron-specific rabies viral glycoprotein (RVG) and glycosylation-stabilized (GNSTM) peptides, allowing the engineered cells to produce and secret exosomes with the RVG and GNSTM peptides on their surface as previously described by Hung, M. E., & Leonard, J. N., 2015. These engineered exosomes were collected then coated onto the surfaces of synthetic nanoparticles using the mechanical method or extrusion. Western blot of exosomes produced from transfected or non-transfected cells and probed with anti-HA antibody against HA tag present in Lamp2b fusion protein are also shown in the figure.