J. Justin Gooding

Nanoparticles that catalyze biochemically relevant reactions are promoted as alternative enzymes. The application of such artificial enzymes is severely restricted by poor selectivity in biological fluids; mainly because the reactions occur at active sites on the exterior surface of the nanoparticle. Enzymes in contrast typically have their active sites down a nanoconfined substrate channel where the reaction occurs in different solution conditions to bulk solution which aids in achieving selectivity for the substrate. Herein the same 3D structure of enzymes is mimicked in nanoparticles to allow selective reactions in biological fluids. This is achieved using a gold nanoparticle coated in a conducting mesoporous carbon shell where isolated nanochannels lead to the gold surface. It can detect glucose in whole blood with no interference from other species. This is achieved by electrochemically pulsing the artificial enzymes to generate the locally required alkalinity for an effective electrocatalytic reaction in the nanochannels, as well as expelling fouling agents that will otherwise passivate the electrocatalytic reaction. The artificial enzymes are shown to be capable of detecting glucose in biological fluids, without loss of signal, for several months. This study shows how nanoconfinement in nanoparticles can be exploited to potentially allow a broad range of species to be selectively detected in biological fluids with stability that can exceed that of enzymes.

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer’s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (Aβ) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-Aβ antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle’s binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI.