Preparation of gold glyconanoparticles (AuGNPs) as theragnostic agents for brain ischemia

The use of nanotechnology in medicine has attracted considerable attention for its potential advances in healthcare to tackle complex issues. Nanoparticles are believed to be capable of solving unmet medical challenges, as they do not follow the common pharmacokinetics and bio-distribution of conventional drugs. Glycans have exploitable properties that make them unique candidates to implement in the field of nanotechnology; merging nanotechnology and glycoscience can bring innovation in the field and their marriage will broaden nanomedicine applications and establish the current ones. Glycans are, among other things, mediators in the interaction between cells; in particular they take part in inflammatory processes. Here, we present a one pot, simple method for the preparation of spherical gold glyconanoparticles (AuGNPs). Surface decoration was achieved with thiol ligands functionalized with carbohydrates and amino groups, the latter for future radiolabelling of the NPs with 18F-labelled prosthetic groups. Carbohydrate ligands were synthesized by reacting (11-(Methylcarbonylthio)undecyl)tetra(ethylene glycol) with fully protected sugars1 (Fig. 1b), while amino ligands were obtained with the Mitsunobu reaction between (11-(Methylcarbonylthio)undecyl)tetra(ethylene glycol) and phthalimide, followed by hydrolysis1 (Fig. 1a). Monodisperse, 2nm sized NPs could be obtained by reduction of HAuCl4 with NaBH4 in CH2Cl2 with addition of the desired ligand (Fig. 1c-d). Future experiments will focus in radiolabelling and determination of the bio-distribution and biological fate of the NPs in healthy rodents using Positron Emission Tomography (PET). Selected glycosylated NPs will be investigated as theragnostic agents in mouse and rat models of cerebral ischemia.